Health Justice in the Context of Health and Human Rights

The inextricable link between the promotion and protection of both health and human rights comes to the fore in the lack of attention to structural determinants in pandemic responses. By requiring that rather than treating everyone the same, additional efforts be made to reach and elevate the most marginalized and discriminated against, human rights incorporate the notion of redistributive justice, expressed by Alang and Blackstock as the need to "ensure access to and redistribution of resources." Linking to the legal basis of the health and human rights framework, the authors also call for the "introduction of mandates and enforcement of regulations that redistribute power"' and for "legislation that guarantees support for people with long-haul COVID-19." The strong history of community organizing and grassroots activism among the human rights community might indeed be leveraged to push for government action and accountability at the local, state, and national levels.

"I Can't Take This Shitty Quarantine Anymore": Sexual Behavior and PrEP Use Among Young Men Who Have Sex with Men and Transgender Women in Brazil During the COVID-19 Pandemic.

This study analyzes how the COVID-19 pandemic affected sexual behavior and use of HIV prevention methods among young transgender women (YTGW) and young gay, bisexual and other men who have sex with men (YGBMSM) participating in an HIV pre-exposure prophylaxis (PrEP) demonstration study in Brazil. Online interviews with 39 participants aged 15-22 years old were conducted between September and November 2020 and analyzed based on social constructionism and human rights-based approaches to health. The pandemic disrupted interviewees' routines, negatively affecting their life conditions. Among those who did not have a steady partner, social distance measures led to temporary interruption of sexual encounters and increased sexting and solo sex. Conversely, for those who had a steady relationship such measures contributed to increasing sexual practices and intimacy. Participants who had sexual encounters during the pandemic reported having continued to use PrEP. However, home confinement with family, lack of privacy, loss of daily routines and changes in housing impaired PrEP adherence and attendance at follow-up consultations. These results highlight the importance of maintaining HIV-service delivery for these groups during a public health crisis, as well as to address the structural drivers of the epidemic with comprehensive HIV prevention policies and by ensuring access of YGBMSM and YTGW to social protection policies.

Law, human rights and gender in practice: an analysis of lessons from implementation of self-care interventions for sexual and reproductive health.

Self-care interventions for health are becoming increasingly available, and among the preferred options, including during the COVID-19 pandemic. This research assessed the extent of attention to laws and policies, human rights and gender in the implementation of self-care interventions for sexual and reproductive health (SRH), to identify where additional efforts to ensure an enabling environment for their use and uptake will be useful. A literature review of relevant studies published between 2010 and 2020 was conducted using PubMed, Scopus and Web of Science. Relevant data were systematically abstracted from 61 articles. In March-April 2021, semi-structured interviews were conducted with 10 key informants, selected for their experience implementing self-care interventions for SRH, and thematically analysed. Laws and policies, rights and gender are not being systematically addressed in the implementation of self-care interventions for SRH. Within countries, there is varied attention to the enabling environment including the acceptability of interventions, privacy, informed consent and gender concerns as they impact both access and use of specific self-care interventions, while other legal considerations appear to have been under-prioritised. Operational guidance is needed to develop and implement supportive laws and policies, as well as to ensure the incorporation of rights and gender concerns in implementing self-care interventions for SRH.

Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography.

Single-domain Variable New Antigen Receptors (VNARs) from the immune system of sharks are the smallest naturally occurring binding domains found in nature. Possessing flexible paratopes that can recognize protein motifs inaccessible to classical antibodies, VNARs have yet to be exploited for the development of SARS-CoV-2 therapeutics. Here, we detail the identification of a series of VNARs from a VNAR phage display library screened against the SARS-CoV-2 receptor binding domain (RBD). The ability of the VNARs to neutralize pseudotype and authentic live SARS-CoV-2 virus rivalled or exceeded that of full-length immunoglobulins and other single-domain antibodies. Crystallographic analysis of two VNARs found that they recognized separate epitopes on the RBD and had distinctly different mechanisms of virus neutralization unique to VNARs. Structural and biochemical data suggest that VNARs would be effective therapeutic agents against emerging SARS-CoV-2 mutants, including the Delta variant, and coronaviruses across multiple phylogenetic lineages. This study highlights the utility of VNARs as effective therapeutics against coronaviruses and may serve as a critical milestone for nearing a paradigm shift of the greater biologic landscape.

Effects of the COVID-19 pandemic on the sexual and mental health of adolescent and adult men who have sex with men and transgender women participating in two PrEP cohort studies in Brazil: COBra study protocol.

INTRODUCTION: The COVID-19 pandemic and its control measures have impacted health and healthcare provision in various levels. Physical distancing measures, for instance, may affect sexual health, impacting access to HIV prevention supplies and changing sexual behaviour, as well as mental health, increasing feelings of unsafety and weakening community support ties. These effects can be worsened among socially marginalised groups, such as men who have sex with men (MSM) and transgender women (TGW). Brazil is among the countries most affected by COVID-19 in the world, where control measures have been inconsistently implemented. We aim to investigate the effects of the COVID-19 pandemic on the sexual and mental health of adolescent and adult MSM and TGW in Brazil. METHODS: Convergent mixed-method prospective cohort study, nested in two ongoing HIV pre-exposure prophylaxis (PrEP) cohorts in Brazil, named PrEP1519 and Combina. Participants will be invited to answer, at baseline and after 6 months, a questionnaire about the effects of the COVID-19 pandemic on sexual behaviour, HIV prevention and mental health. Data on HIV infection and sexually transmitted infections (STI) will be collected as part of routine follow-up from the cohorts. Main outcome measures (HIV infection, STI and depression symptoms) will be observed within 12 months after baseline. Sample size is estimated at 426 participants. Complementarily, 50 participants will be invited to in-depth interviews through video calls or interactive voice response, and 20 will be invited to chronicle their lives during the pandemic through digital diaries. Triangulation will be done across qualitative methods and with the quantitative data. ETHICS AND DISSEMINATION: The study was approved by Research Ethics Committees from the Brazilian Universities coordinating the study. Findings will be published in scientific journals and presented at meetings. Informative flyers will be elaborated to communicate study findings to participants and key stakeholders.

The COVID-19 Drug and Gene Set Library.

In a short period, many research publications that report sets of experimentally validated drugs as potential COVID-19 therapies have emerged. To organize this accumulating knowledge, we developed the COVID-19 Drug and Gene Set Library (https://amp.pharm.mssm.edu/covid19/), a collection of drug and gene sets related to COVID-19 research from multiple sources. The platform enables users to view, download, analyze, visualize, and contribute drug and gene sets related to COVID-19 research. To evaluate the content of the library, we compared the results from six in vitro drug screens for COVID-19 repurposing candidates. Surprisingly, we observe low overlap across screens while highlighting overlapping candidates that should receive more attention as potential therapeutics for COVID-19. Overall, the COVID-19 Drug and Gene Set Library can be used to identify community consensus, make researchers and clinicians aware of new potential therapies, enable machine-learning applications, and facilitate the research community to work together toward a cure.

The COVID-19 Gene and Drug Set Library.

The coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 (COVID-19) pandemic has received rapid response by the research community to offer suggestions for repurposing of approved drugs as well as to improve our understanding of the COVID-19 viral life cycle molecular mechanisms. In a short period, tens of thousands of research preprints and other publications have emerged including those that report lists of experimentally validated drugs and compounds as potential COVID-19 therapies. In addition, gene sets from interacting COVID-19 virus-host proteins and differentially expressed genes when comparing infected to uninfected cells are being published at a fast rate. To organize this rapidly accumulating knowledge, we developed the COVID-19 Gene and Drug Set Library (https://amp.pharm.mssm.edu/covid19/), a collection of gene and drug sets related to COVID-19 research from multiple sources. The COVID-19 Gene and Drug Set Library is delivered as a web-based interface that enables users to view, download, analyze, visualize, and contribute gene and drug sets related to COVID-19 research. To evaluate the content of the library, we performed several analyses including comparing the results from 6 in-vitro drug screens for COVID-19 repurposing candidates. Surprisingly, we observe little overlap across these initial screens. The most common and unique hit across these screen is mefloquine, a malaria drug that should receive more attention as a potential therapeutic for COVID-19. Overall, the library of gene and drug sets can be used to identify community consensus, make researchers and clinicians aware of the development of new potential therapies, as well as allow the research community to work together towards a cure for COVID-19.

Targeting drug delivery in the vascular system: Focus on endothelium.

The bloodstream is the main transporting pathway for drug delivery systems (DDS) from the site of administration to the intended site of action. In many cases, components of the vascular system represent therapeutic targets. Endothelial cells, which line the luminal surface of the vasculature, play a tripartite role of the key target, barrier, or victim of nanomedicines in the bloodstream. Circulating DDS may accumulate in the vascular areas of interest and in off-target areas via mechanisms bypassing specific molecular recognition, but using ligands of specific vascular determinant molecules enables a degree of precision, efficacy, and specificity of delivery unattainable by non-affinity DDS. Three decades of research efforts have focused on specific vascular targeting, which have yielded a multitude of DDS, many of which are currently undergoing a translational phase of development for biomedical applications, including interventions in the cardiovascular, pulmonary, and central nervous systems, regulation of endothelial functions, host defense, and permeation of vascular barriers. We discuss the design of endothelial-targeted nanocarriers, factors underlying their interactions with cells and tissues, and describe examples of their investigational use in models of acute vascular inflammation with an eye on translational challenges.