RESUMO
The adaptive immune system protects against infection via selection of specific antigen receptors on B-cells and T-cells. We studied the prevalent CD8 killer T-cell response mounted against SARS-CoV-2 Spike269-277 epitope YLQPRTFLL via the most frequent Human Leukocyte Antigen (HLA) class I worldwide, HLA A*02. The widespread Spike P272L mutation has arisen in at least 14 different SARS-CoV-2 lineages to date, including in lineages identified as variants of concern. P272L was common in the B.1.177 lineage associated with establishing the second wave in Europe. The large CD8 T-cell response seen across a cohort of HLA A*02+ convalescent patients, comprising of over 120 different TCRs, failed to respond to the P272L. Sizable populations (0.01%-0.2%) of total CD8 T-cells from individuals vaccinated against SARS-CoV-2 stained with HLA A*02-YLQPRTFLL multimers but failed to bind to the P272L reagent. Viral escape at prevalent T-cell epitopes restricted by high frequency HLA may be particularly problematic when vaccine immunity is focussed on a single protein such as SARS-CoV-2 Spike and provides a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlights the urgent need for monitoring T-cell escape in new SARS-CoV-2 variants. New in Version 2O_LIUpdated as P272L now seen in 14 different SARS-CoV-2 lineages including the B.1.1.7/Alpha (UK variant) lineage C_LIO_LIAtomic structures of HLA A*02-YLQPRTFLL and HLA A*02-YLQLRTFLL added C_LIO_LIPierre Rizkallah added as an author and author list changed to reflect the contributions of Aaron Wall and Anna Fuller to the newly added datasets C_LI
RESUMO
Two cats from different COVID-19-infected households in the UK were found to be infected with SARS-CoV-2 from humans, demonstrated by immunofluorescence, in situ hybridisation, reverse transcriptase quantitative PCR and viral genome sequencing. Lung tissue collected post-mortem from cat 1 displayed pathological and histological findings consistent with viral pneumonia and tested positive for SARS-CoV-2 antigens and RNA. SARS-CoV-2 RNA was detected in an oropharyngeal swab collected from cat 2 that presented with rhinitis and conjunctivitis. High throughput sequencing of the virus from cat 2 revealed that the feline viral genome contained five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS-CoV-2 sequence. An analysis of cat 2s viral genome together with nine other feline-derived SARS-CoV-2 sequences from around the world revealed no shared catspecific mutations. These findings indicate that human-to-cat transmission of SARS-CoV-2 occurred during the COVID-19 pandemic in the UK, with the infected cats developing mild or severe respiratory disease. Given the versatility of the new coronavirus, it will be important to monitor for human-to-cat, cat-to-cat and cat-to-human transmission.
