Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope.

We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein269-277 epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A∗02. The Spike P272L mutation that has arisen in at least 112 different SARS-CoV-2 lineages to date, including in lineages classified as "variants of concern," was not recognized by the large CD8 T cell response seen across cohorts of HLA A∗02+ convalescent patients and individuals vaccinated against SARS-CoV-2, despite these responses comprising of over 175 different individual T cell receptors. Viral escape at prevalent T cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focused on a single protein such as SARS-CoV-2 Spike, providing a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlighting the need for monitoring T cell escape in new SARS-CoV-2 variants.

Management of Acute Appendicitis in Children During COVID-19 and Perspectives of Pediatric Surgeons From South Asia: Survey Study.

BACKGROUND: Nonoperative treatment (NOT) of pediatric appendicitis as opposed to surgery elicits great debate and is potentially influenced by physician preferences. Owing to the effects of the COVID-19 pandemic on health care, the practice of NOT has generally increased by necessity and may, in a post-COVID-19 world, change surgeons' perceptions of NOT. OBJECTIVE: The aim of this study was to determine whether the use of NOT has increased in South Asia and whether these levels of practice would be sustained after the pandemic subsides. METHODS: A survey was conducted among pediatric surgeons regarding their position, institute, and country; the number of appendicitis cases they managed; and their mode of treatment between identical time periods in 2019 and 2020 (April 1 to August 31). The survey also directly posed the question as to whether they would continue with the COVID-19-imposed level of NOT after the effect of the pandemic diminishes. RESULTS: A total of 134 responses were collected out of 200 (67.0%). A significant increase in the practice of NOT was observed for the entire cohort, although no effect was observed when grouped by country or institute. When grouped by position, senior physicians increased the practice of NOT the most, while junior physicians reported the least change. The data suggest that only professors would be inclined to maintain the COVID-19-level of NOT practice after the pandemic. CONCLUSIONS: Increased practice of NOT during the COVID-19 pandemic was observed in South Asia, particularly by senior surgeons. Only professors appeared inclined to consider maintaining this increased level of practice in the post-COVID-19 world.