T cell-mediated immunity may play a critical role in controlling and establishing protective immunity against SARS-CoV-2 infection; yet the repertoire of viral epitopes responsible for T cell response activation remains mostly unknown. Identification of viral peptides presented on class I human leukocyte antigen (HLA-I) can reveal epitopes for recognition by cytotoxic T cells and potential incorporation into vaccines. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two human cell lines at different times post-infection using mass spectrometry. We found HLA-I peptides derived not only from canonical ORFs, but also from internal out-of-frame ORFs in Spike and Nucleoprotein not captured by current vaccines. Proteomics analyses of infected cells revealed that SARS-CoV-2 may interfere with antigen processing and immune signaling pathways. Based on the endogenously processed and presented viral peptides that we identified, we estimate that a pool of 24 peptides would provide one or more peptides for presentation by at least one HLA allele in 99% of the human population. These biological insights and the list of naturally presented SARS-CoV-2 peptides will facilitate data-driven selection of peptides for immune monitoring and vaccine development.
Four emergency shelters were instituted in Lisbon during COVID-19, and are still in operation. Between March and August 2020, they served over 600 people. The shelters host a diverse population, including people experiencing homelessness, foreigners, LGBTI + people, those with reduced mobility, couples, those with pets, and People Who Use Drugs, including alcohol (henceforth PWUD). Individuals are provided care regardless of their immigration or residence status. In order to ensure continuity of care in the shelters and to bring in clients who usually refuse to be sheltered, a range of social and health interventions are integrated into the shelters. Harm reduction services ensure that the most vulnerable populations, PWUD and people experiencing homelessness, have access to the services they need. Innovations in service provision maximize the services impacts and pave the way for the future inclusion and development of these services.
Background Subarachnoid hemorrhage (SAH) survivors experience significant neurological disability, some of which is under‐recognized by neurovascular clinical teams. We set out to objectively determine the occurrence of hearing impairment after SAH, characterize its peripheral and/or central origin, and investigate likely pathological correlates. Methods In a case‐control study (n = 41), participants were asked about new onset hearing difficulty 3 months post‐SAH, compared with pre‐SAH. Formal audiological assessment included otoscopy, pure tone audiometry, a questionnaire identifying symptoms of peripheral hearing loss and/or auditory processing disorder, and a test of speech understanding in noise. A separate cohort (n = 21) underwent quantitative susceptibility mapping (QSM) of the auditory cortex 6 months after SAH, for correlation with hearing difficulty. Results Twenty three percent of SAH patients reported hearing difficulty that was new in onset post‐SAH. SAH patients had poorer pure tone thresholds compared to controls. The proportion of patients with peripheral hearing loss as defined by the World Health Organization and British Audiological Society was however not increased, compared to controls. All SAH patients experienced symptoms of auditory processing disorder post‐SAH, with speech‐in‐noise test scores significantly worse versus controls. Iron deposition in the auditory cortex was higher in patients reporting hearing difficulty versus those who did not. Conclusion This study firmly establishes hearing impairment as a frequent clinical feature after SAH. It primarily consists of an auditory processing disorder, mechanistically linked to iron deposition in the auditory cortex. Neurovascular teams should inquire about hearing, and refer SAH patients for audiological assessment and management.
Background Ahead of opening Portugal’s first mobile drug consumption room (MDCR) in Lisbon, information from People Who Use Drugs (PWUD) and local community members was necessary to determine current needs and shape the intervention. A participatory and peer-led process was ensured at all stages of data gathering and planning of the intervention. Methods Prospective clients were surveyed to determine their willingness to use the service and preferences for use and to gain sociodemographic information. Persons over the age of 18 who reported injection drug use (PWID) were recruited using convenience sampling in the main open drug use scenes in Lisbon. In-person interviews were conducted by trained peer workers between November and December of 2017. The results ( n = 72) of the questionnaires were analyzed, providing descriptive statistics. Results There is a high level of willingness to use the MDCR, primarily for reasons of hygiene, privacy, and security. Most participants expressed a desire to use the MDCR daily. Potential clients are socially marginalized, and many suffer from unstable housing. Most are daily users and engage in unsafe injecting practices, such as public injecting and material sharing. High levels of hepatitis C, HIV, and hepatitis B were observed among the target population with low levels of healthcare access and utilization. Preferences were gauged regarding the scheduling of the MDCR’s hours and amount of time willing to travel to reach the MDCR and will be taken into account for implementation. The combination of high levels of willingness to utilize the service and high levels of need among the target population support the implementation of Lisbon’s first MDCR. Conclusions Continual participation of PWUD and other community members will be necessary to maximize the public health and social impacts of this intervention, relative to this baseline. The plan to continue the participatory and peer-led development of the MDCR includes integrating peer workers, clients, and local community members within the operation, management, and evaluation of the service. This research adds to a growing literature about drug consumption rooms (DCRs) in Europe, which is especially limited concerning MDCRs.
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