RESUMO
Background: Healthcare Information for All (HIFA) is a multidisciplinary global campaign consisting of more than 20,000 members worldwide committed to improving the availability and use of health care information in low- and middle-income countries (LMICs). During the COVID-19 pandemic, online HIFA forums saw a tremendous amount of discussion regarding the lack of information about COVID-19, the spread of misinformation, and the pandemic's impact on different communities. Objective: This study aims to analyze the themes and perspectives shared in the COVID-19 discussion on English HIFA forums. Methods: Over a period of 8 months, a qualitative thematic content analysis of the COVID-19 discussion on English HIFA forums was conducted. In total, 865 posts between January 24 and October 31, 2020, from 246 unique study participants were included and analyzed. Results: In total, 6 major themes were identified: infodemic, health system, digital health literacy, economic consequences, marginalized peoples, and mental health. The geographical distribution of study participants involved in the discussion spanned across 46 different countries in every continent except Antarctica. Study participants' professions included public health workers, health care providers, and researchers, among others. Study participants' affiliation included nongovernment organizations (NGOs), commercial organizations, academic institutions, the United Nations (UN), the World Health Organization (WHO), and others. Conclusions: The themes that emerged from this analysis highlight personal recounts, reflections, suggestions, and evidence around addressing COVID-19 related misinformation and might also help to understand the timeline of information evolution, focus, and needs surrounding the COVID-19 pandemic.
RESUMO
Stress is known to impede certain host defense mechanisms, including those governed by conventional T lymphocytes. However, whether innate-like T lymphocytes, such as invariant natural killer T (iNKT) and mucosa-associated invariant T (MAIT) cells, are impacted by stress is unclear. Herein, we report that prolonged psychological stress caused by physical confinement results in robust upregulation of T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), an immune checkpoint receptor that controls antitumor and antiviral immune responses. Elevated TIGIT expression was found not only on NK and conventional T cells, but also on iNKT and MAIT cells. Stress-provoked TIGIT upregulation was reversed through treatment with the glucocorticoid receptor (GR) antagonist RU486, but not with 6-hydroxydopamine that induces chemical sympathectomy. A Cre/Lox gene targeting model in which GR was ablated in cells expressing Lck under its proximal promoter revealed that TIGIT upregulation in stressed animals stems from direct GR signaling in T and iNKT cells. In fact, long-term oral administration of exogenous corticosterone (CS) to wild-type C57BL/6 (B6) mice was sufficient to increase TIGIT expression levels on T and iNKT cells. In vitro treatment with CS also potently and selectively upregulated TIGIT, but not CTLA-4 or LAG-3, on mouse iNKT and MAIT hybridomas. These results were recapitulated using primary hepatic iNKT and MAIT cells from wild-type B6 and B6.MAITCAST mice, respectively. Subjecting B6.MAITCAST mice to physical restraint also raised the frequency of TIGIT+ cells among hepatic MAIT cells in a GR-dependent manner. Finally, we found that TIGIT is similarly upregulated in a chronic variable stress model in which animals are exposed to unpredictable heterotypic stressors without developing habituation. Taken together, our findings link, for the first time to our knowledge, GR signaling to TIGIT expression. We propose that glucocorticoid hormones dampen immune responses, in part, by enhancing TIGIT expression across multiple critical subsets of effector lymphocytes, including innate-like T cells. Therefore, TIGIT may constitute an attractive target in immune-enhancing interventions for sustained physiological stress.
