SARS-CoV-2 antagonises the cellular interferon response, but whether the virus manipulates cellular immunity is unclear. An unbiased proteomic approach to determine how cell surface protein expression is altered on SARS-CoV-2-infected lung epithelial cells showed downregulation of activating NK cell ligands: B7-H6, MICA, ULBP2, and Nectin1, but no effect on surface MHC-I expression. NK ligand downregulation correlated with a reduction in NK cell activation by infected cells, and was overcome by antibody-dependent NK cell activation (ADNKA). Depletion of spike-specific antibodies confirmed their dominant role in virus neutralisation, but these antibodies played only a minor role in ADNKA compared to antibodies to other viral proteins, including ORF3a, Membrane, and Nucleocapsid. In contrast, ADNKA induced following vaccination was focussed solely on spike, was weaker than ADNKA following natural infection, and was not boosted by the second dose. These insights have important implications for understanding disease progression, vaccine efficacy, and vaccine design.
Introduction: There is increasing need for renal replacement therapy associated with the aging population and dramatic increases in diabetes prevalence. Despite an increasing clinical vascular access workload, there are significant unanswered research questions and a paucity of high quality trials to guide clinical practice. To address where future research in vascular access should be directed, we conducted a Priority Setting Partnership involving multiple disciplines, specialties, patients and carers. Methods: In collaboration with the James Lind Alliance, four rounds of surveys were circulated to identify and score professional and patient priorities in vascular access research. Finally, in a consensus workshop attended by patients and professionals, priorities were discussed and a ranked top 10 list was produced using a nominal group technique. Results: A total of 1,813 research priorities were submitted within all areas of vascular surgery. Following removal of duplicates, consolidation and categorisation, 15 patient and professional priorities in vascular access research were taken forward to the consensus workshop. The workshop produced a ranked top 10 list of vascular access research priorities relating to: optimising access function, preventing access complications and education of patients and healthcare staff. Conclusions: These research priorities should help to direct and contextualise future research in vascular access.
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