Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19.

Although the importance of virus-specific cytotoxic T lymphocytes (CTL) in virus clearance is evident in COVID-19, the characteristics of virus-specific CTLs related to disease severity have not been fully explored. Here we show that the phenotype of virus-specific CTLs against immunoprevalent epitopes in COVID-19 convalescents might differ according to the course of the disease. We establish a cellular screening method that uses artificial antigen presenting cells, expressing HLA-A*24:02, the costimulatory molecule 4-1BBL, SARS-CoV-2 structural proteins S, M, and N and non-structural proteins ORF3a and nsp6/ORF1a. The screen implicates SARS-CoV-2 M protein as a frequent target of IFNγ secreting CD8+ T cells, and identifies M198-206 as an immunoprevalent epitope in our cohort of HLA-A*24:02 positive convalescent COVID-19 patients recovering from mild, moderate and severe disease. Further exploration of M198-206-specific CD8+ T cells with single cell RNA sequencing reveals public TCRs in virus-specific CD8+ T cells, and shows an exhausted phenotype with less differentiated status in cells from the severe group compared to cells from the moderate group. In summary, this study describes a method to identify T cell epitopes, indicate that dysfunction of virus-specific CTLs might be an important determinant of clinical outcomes.

The retroperitoneal interfascial planes: current overview and future perspectives.

Recently, the concept of interfascial planes has become the prevalent theory among radiologists for understanding the retroperitoneal anatomy, having replaced the classic tricompartmental theory. However, it is a little known fact that the concept remains incomplete and includes embryological errors, which have been revised on the basis of our microscopic study. We believe that the concept not only provides a much clearer understanding of the retroperitoneal anatomy, but it also allows further development for diagnosis and treatment of retroperitoneal injuries and diseases, should it become an accomplished theory. We explain the history and outline of the concept of interfascial planes, correct common misunderstandings about the concept, explain the unconsciously applied therapeutic procedures based on the concept, and present future perspectives of the concept using our published and unpublished data. This knowledge could be essential to acute care physicians and surgeons sometime soon.