Factors associated with COVID-19 vaccine intentions during the COVID-19 pandemic; a systematic review and meta-analysis of cross-sectional studies.

BACKGROUND: A high COVID-19 vaccine uptake is essential to achieve herd immunity to combat the current strain of COVID-19 and potential future variants. This review aimed to identify factors associated with public intention to receive COVID-19 vaccines until February 2021 to provide accessible data to policymakers to inform framing and targeting of messages designed to optimise vaccine uptake. METHODS: Medline, Embase, CINAHL, PsycINFO, PsycARTICLES, Sociological Abstracts and Applied Social Sciences Index and Abstracts were searched for cross-sectional studies reporting data regarding COVID-19 vaccine intentions, published between 01/01/2020 and 12/02/2021. Title/abstract and full-text screening were performed independently by two authors. The Appraisal Tool for Cross-sectional Studies (AXIS) was used to assess bias and quality. Both random-effects meta-analysis and narrative synthesis were used to describe vaccine intentions and associated factors. A subgroup analysis assessing the impact of sex, sampling method and time of survey on COVID-19 vaccine intention was performed. RESULTS: Searches identified 4739 studies, and 23 cross-sectional studies were deemed eligible for the review; 22 used online surveys and one used a mixed-methods study design. Eighteen surveys were conducted in the first half of 2020 and five were conducted in the latter half of 2020. Fifteen countries were represented, with the most common being the United States (n = 4) and the United Kingdom (n = 4) sampling 41,403 participants across all surveys. Most studies employed convenience sampling and 11 non-responder rates raised concerns over non-response bias. From the 18 studies included in the meta-analysis, the pooled proportion of survey participants willing to receive the COVID-19 vaccine was 73.3% (n = 18, 95% Confidence Interval 64.2 to 81.5%, I2 = 99.7%). Factors associated with a higher COVID-19 vaccine acceptance included greater perceived risk of COVID-19, lower level of perceived vaccine harm, higher educational attainment and household income, older age, being of White ethnicity and male sex. CONCLUSIONS: There was a high willingness to receive the COVID-19 vaccine which was influenced by sociodemographic factors and risk perceptions. The findings suggest future research should explore reasoning behind vaccine intentions for different sociodemographic groups to allow targeted communication strategies to be formulated by public health agencies. REGISTRATION: PROSPERO Registration Number: CRD42021239134.

Adaptations in clinical examinations of medical students in response to the COVID-19 pandemic: a systematic review.

INTRODUCTION: Clinical examinations (assessments) are integral to ensuring that medical students can treat patients safely and effectively. The COVID-19 pandemic disrupted traditional formats of clinical examinations. This prompted Medical Schools to adapt their approaches to conducting these examinations to make them suitable for delivery in the pandemic. This systematic review aims to identify the approaches that Medical Schools, internationally, adopted in adapting their clinical examinations of medical students in response to the COVID-19 pandemic. METHODS: Three databases and four key medical education journals were systematically searched up to 22 October 2021; a grey literature search was also undertaken. Two reviewers independently screened at title, abstract stage and full text stage against predefined eligibility criteria. Discrepancies were resolved by discussion and involvement of senior authors. Risk of bias assessment was performed using an adapted version of a pre-existing risk of bias assessment tool for medical education developments. Results were summarised in a narrative synthesis. RESULTS: A total of 36 studies were included, which documented the approaches of 48 Medical Schools in 17 countries. Approaches were categorised into in-person clinical examinations (22 studies) or online clinical examinations (14 studies). Authors of studies reporting in-person clinical examinations described deploying enhanced infection control measures along with modified patient participation. Authors of studies reporting online clinical examinations described using online software to create online examination circuits. All authors reported that adapted examinations were feasible, scores were comparable to previous years' student cohorts, and participant feedback was positive. Risk of bias assessment highlighted heterogeneity in reporting of the clinical examinations. CONCLUSIONS: This review identified two broad approaches to adapting clinical examinations in the pandemic: in-person and online. Authors reported it was feasible to conduct clinical examinations in the pandemic where medical educators are given sufficient time and resources to carefully plan and introduce suitable adaptations. However, the risk of bias assessment identified few studies with high reporting quality, which highlights the need for a common framework for reporting of medical education developments to enhance reproducibility across wider contexts. Our review provides medical educators with the opportunity to reflect on past practises and facilitate the design and planning of future examinations.

Changes in the activity of the GPx-1 anti-oxidant selenoenzyme in mononuclear cells following imatinib treatment.

Imatinib inhibits the ABL tyrosine kinase and is effective for the treatment of chronic myeloid leukemia (CML). ABL activates GPx-1, an enzyme associated with protection against oxidative DNA damage and disease. Enzyme activity was assessed in sample pairs consisting of mononuclear cells obtained from patients before and after imatinib therapy. Control sample sets obtained from patients not receiving imatinib showed little change in GPx activity over a several month interval. Five of 7 sample sets obtained from imatinib-receiving patients showed changes in GPx activity greater than 30%. One sample decreased 42% while 4 others increased 33-208%. Patients with the largest increase in activity were female and had the lowest baseline levels of GPx activity. Changes in GPx activity may influence the clinical outcome of patients being treated for CML.

Modulation of experimental autoimmune encephalomyelitis by VLA-2 blockade.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Adhesion molecules play important roles in cell-cell and cell-extracellular matrix (ECM) interactions in inflammation. Blocking the interaction between inflammatory cells and vascular endothelia can prevent cell entry into tissues and harmful inflammatory responses, that is, autoimmunity, but could also limit immunosurveillance by anti-viral T cells in sites of infection or latency. Development of progressive multifocal leukoencephalopathy in patients treated with antibody against very late antigen (VLA)-4 prompted us to explore an alternative therapeutic approach. We used an antibody against the integrin alpha2, VLA-2, that interacts with ECM, not vascular endothelium. SJL/J mice were sensitized with myelin proteolipid protein (PLP)(139-151) peptide to induce experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Treatment of mice with VLA-2 antibody suppressed clinical signs and CNS inflammation of EAE, when antibody was given immediately after disease onset. In contrast, VLA-4 or VLA-2 antibody treatment of mice during the priming or remission phase of EAE had minor effects on the disease's clinical course. No differences were found in lymphoproliferative responses to PLP(139-151) among treatment groups. Data suggest that blocking cell-ECM interactions can be an alternative therapy for MS.

Contrasting roles for axonal degeneration in an autoimmune versus viral model of multiple sclerosis: When can axonal injury be beneficial?

Although demyelination is a cardinal feature in multiple sclerosis, axonal injury also occurs. We tested whether a delay in axonal degeneration could affect the disease severity in two models for multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus (TMEV) infection. We compared wild-type C57BL/6 (B6) mice with C57BL/Wld(s) (Wld) mice, which carry a mutation that delays axonal degeneration. In EAE, both mouse strains were sensitized with myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide and showed a similar disease onset, MOG-specific lymphoproliferative responses, and inflammation during the acute stage of EAE. However, during the chronic stage, B6 mice continued to show paralysis with a greater extent of axonal damage, demyelination, and MOG-specific lymphoproliferative responses compared with Wld mice, which showed complete recovery. In TMEV infection, only Wld mice were paralyzed and had increased inflammation, virus antigen-positive cells, and TMEV-specific lymphoproliferative responses versus infected B6 mice. Because TMEV can use axons to disseminate in the brain, axonal degeneration in B6 mice might be a beneficial mechanism that limits the virus spread, whereas slow axonal degeneration in Wld mice could favor virus spread. Therefore, axonal degeneration plays contrasting roles (beneficial versus detrimental) depending on the initiator driving the disease.

Massive apoptosis in lymphoid organs in animal models for primary and secondary progressive multiple sclerosis.

The mechanism(s) responsible for generating the different forms of multiple sclerosis, primary progressive (PP) and secondary progressive (SP) versus relapsing-remitting (RR), is not well understood. Using myelin oligodendrocyte glycoprotein (MOG)(92-106), we have established animal models that mimic the different types of multiple sclerosis. A.SW mice develop PP or SP-experimental allergic encephalomyelitis (EAE) with large areas of demyelination and high titers of MOG antibody whereas SJL/J mice develop RR-EAE with perivascular T cells and mild demyelination. In A.SW progressive EAE, we found atrophy of the thymus, spleen, and lymph nodes with depletion of T and B cells and massive apoptosis, as demonstrated by immunohistochemistry, terminal dUTP nick-end labeling, and DNA agarose gel electrophoresis. To test whether lymphoid apoptosis itself contributes to disease progression, we injected SJL/J mice with apoptotic thymocytes. Injection of apoptotic cells resulted in greater than 20% of mice developing SP-EAE with ataxia. SJL/J mice with SP-EAE had large areas of demyelination, high MOG antibody titers and atrophic lymphoid organs. Spleen cells from mice with progressive EAE produced less interferon-gamma than those from RR-EAE when stimulated with mitogen. We suggest that induction of lymphoid apoptosis alters the balance of Th1 versus Th2 immune responses and increases MOG antibody production, leading to exacerbation of demyelination and subsequent disease progression.