ABSTRACT
A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of ORF7a: H47Y mutation. Here we evaluated the effect of this mutation on the three main functions ascribed to SARS-CoV-2 ORF7a protein. Our findings show that H47Y mutation impairs the ability of SARS-CoV-2 ORF7a to antagonize type-I interferon (IFN-I) response and to downregulate Major Histocompatibility Complex-I (MHC-I) cell surface levels, but had no effect in its anti-SERINC5 function. Overall, our results suggest that the H47Y mutation of ORF7a affects important functions of this protein resulting in changes in virus pathogenesis.
ABSTRACT
Background Urgent Suspected Cancer (Two Week Wait, 2WW) referrals have improved early cancer detection but are increasingly a major burden on NHS services. This has been exacerbated by the COVID-19 pandemic. Method We developed and validated tests to assess the risk of any cancer for 2WW patients. The tests use routine blood measurements (FBC, U&E, LFTs, tumour markers), combining them using machine learning and statistical modelling. Algorithms were developed and validated for nine 2WW pathways using retrospective data from 371,799 referrals to Leeds Teaching Hospitals Trust (development set 224,669 referrals, validation set 147,130 referrals). A minimum set of blood measurements were required for inclusion, and missing data were modelled internally by the algorithms. Results We present results for two clinical use-cases. In use-case 1, the algorithms identify 20% of patients who do not have cancer and may not need an urgent 2WW referral. In use-case 2, they identify 90% of cancer cases with a high probability of cancer that could be prioritised for review. Conclusions Combining a panel of widely available blood markers produces effective blood tests for cancer for NHS 2WW patients. The tests are affordable, can be deployed rapidly to any NHS pathology laboratory with no additional hardware requirements.