Highlights d Blood cell traits differ by ancestry and are subject to selective pressure d We assessed 15 blood cell traits in 746,667 participants from 5 global populations d We identified more than 5,500 associations, including 100 associations not found in Europeans d These analyses improved risk prediction and identified potential causal variants

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BackgroundThe COVID-19 pandemic has strained healthcare systems and how best to address post-COVID health needs is uncertain. Here we describe the post-COVID symptoms of 675 patients followed up using a virtual review pathway, stratified by severity of acute COVID infection. MethodsCOVID-19 survivors completed an online/telephone questionnaire of symptoms after 12+ weeks and a chest radiograph. Dependent on findings at virtual review, patients were provided information leaflets, attended for investigations and/or were reviewed face-to-face. Outcomes were compared between patients following high-risk and low-risk admissions for COVID pneumonia, and community referrals. ResultsPatients reviewed after hospitalisation for COVID pneumonia had a median of two ongoing physical health symptoms post-COVID. The most common was fatigue (50.3% of highrisk patients). Symptom burden did not vary significantly by severity of hospitalised COVID pneumonia but was highest in community referrals. Symptoms suggestive of depression, anxiety and post-traumatic stress disorder were common (depression occurred in 24.9% of high-risk patients). Asynchronous virtual review facilitated triage of patients at highest need of face-to-face review. ConclusionMany patients continue to have a significant burden of post-COVID symptoms irrespective of severity of initial pneumonia. How best to assess and manage long COVID will be of major importance over the next few years.

Why was the cohort set up?East London Genes & Health (ELGH) is a community based, long-term study of health and disease in British-Bangladeshi and British-Pakistani people in east London. ELGH has a population-based design incorporating cutting-edge genomics with electronic health record (EHR) data linkage and targeted recall-by-genotype (RbG) studies. ELGH currently has >34,000 volunteers with funding to expand to 100,000 volunteers by 2023. ELGH is an open access data resource, and its research will impact a population at high need and redress the poor representation of non-White ethnic groups in existing population genomic cohorts 1 .Almost a quarter of the world's population, and 5% of the UK population, are of South Asian origin 2 .The risk of coronary heart disease is 3-4 times higher, and type 2 diabetes (T2D) 2-4 times higher in UK South Asians compared with Europeans 3,4 . East London incorporates one of the UK's largest South Asian communities (29% of 1.95 million people), of which 70% are British-Bangladeshi and British-Pakistani, and its population live in high levels of deprivation (Tower Hamlets, Hackney, Barking and Dagenham are the 9 th , 10 th and 11 th most deprived local authorities in England) 5 . Compared to White Europeans, South Asians living in east London have a two-fold greater risk of developing T2D 6 , nearly double the risk of non-alcoholic liver disease 7 , and over double the risk of multimorbidity 8 , with the onset of cardiovascular disease occurring 8 years earlier in men 8 . Determinants of poor cardiometabolic health start early in the life course, with higher rates of overweight and obese children in east London compared to the UK average 5 .Recent genomic advances offer exciting potential to better understand the genetic causation of disease 9 , and to direct pharmacotherapy to rare loss-of-function gene variants 10 . Genetic variation relevant to British-Bangladeshi and British-Pakistani populations, such as autozygosity arising from parental relatedness, is under-researched with regards to potential effects on complex adult phenotypes at a population level 11,12 .ELGH fosters authentic, inclusive, long-term engagement in its research, to deliver future health benefits to the population it represents. Community involvement in ELGH helps prioritise areas for

Individuals with South Asian ancestry have a higher risk of heart disease than other groups but have been largely excluded from genetic research. Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort, we conducted genome-wide association studies of coronary artery disease and its key risk factors. Using power-adjusted transferability ratios, we found evidence for transferability for the majority of cardiometabolic loci powered to replicate. The performance of polygenic scores was high for lipids and blood pressure, but lower for BMI and coronary artery disease. Adding a polygenic score for coronary artery disease to clinical risk factors showed significant improvement in reclassification. In Mendelian randomisation using transferable loci as instruments, our findings were consistent with results in European-ancestry individuals. Taken together, trait-specific transferability of trait loci between populations is an important consideration with implications for risk prediction and causal inference.

Documentation of appropriate escalation of treatment was identified as a problem for junior doctors and Critical Care Outreach Nurses at Musgrove Park Hospital. An audit of resuscitation and escalation documentation of all wards found that of the patients who were not for Cardiopulmonary resuscitation (and therefore not for full escalation of care), 78.4% had no documentation of the appropriate level of escalation of treatment should they deteriorate. The majority of junior doctors had experienced cases where they felt that inappropriate treatment had been given, where no escalation plan was documented.Using several Plan, Do, Study, Act (PDSA) cycles, drawing tools used in other trusts and departments, and the views of clinicians, we developed a treatment escalation plan (TEP) tool, to be included in the resuscitation form. This included consideration of referral to critical care, ward based non-invasive ventilation, and appropriate use of intravenous or oral antibiotics. This then prompted the responsible clinician to consider and document appropriate escalation of treatment.The CPR-TEP form was trialed using a quasi-experiment design allowing the aim to be tested using two groups -intervention and control. All patients in the intervention group were not for CPR and therefore had their TEP-CPR form filled in fully (n= 68). The control group consisted of patients who were not for CPR but who did not have a TEP form filled in (n=36).The appropriateness of OOH (out of hours) treatment in those patients who experienced clinical deterioration was judged by questionnairebased feedback from the in-hours team the following morning. Levels of inappropriate treatment between the two groups were compared to test the aim.At the end of the study period, questionnaire feedback indicated that 11.1% of patients in the group with the new CPR-TEP document had received inappropriate OOH care compared to 44.4% of patients in the group without the document. Within working hours there is greater opportunity to explore these factors, and often it is possible for in-hours teams to identify patients at foreseeable risk of deterioration. In these patients, documentation of any inappropriate treatments allows the in-hours team to tailor care to the individual's clinical circumstances and guide out-of-hours (OOH) management, thus promoting beneficence. Our preliminary research suggested that the resuscitative treatment modalities used OOH in patients categorised 'not for CPR', was sometimes considered by in-hours teams to conflict with best interests.

Background: Individuals with South Asian ancestry have higher risk of heart disease than other groups in Western countries; however, most genetic research has focused on European-ancestry (EUR) individuals. It is unknown whether reported genetic loci and polygenic scores (PGSs) for cardiometabolic traits are transferable to South Asians, and whether PGSs have utility in clinical settings. Methods: Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort (G&H), we conducted genome-wide association studies (GWAS) and characterised the genetic architecture of coronary artery disease (CAD), body mass index (BMI), lipid biomarkers and blood pressure. We applied a new technique to assess the extent to which loci from GWAS in EUR samples were transferable. We tested how well existing findings from EUR studies performed in genetic risk prediction and Mendelian randomisation in G&H. Results: Trans-ancestry genetic correlations between G&H and EUR samples for the tested traits were not significantly lower than 1, except for BMI (rg=0.85, p=0.02). We found evidence for transferability for the vast majority of loci from EUR discovery studies that were sufficiently powered to replicate in G&H. PGSs showed variable transferability in G&H, with the relative accuracy compared to EUR (ratio of incremental r2/AUC) ≥0.95 for HDL-C, triglycerides, and blood pressure, but lower for BMI (0.78) and CAD (0.42). We observed significant improvement in categorical net reclassification in G&H (NRI=3.9%; 95% CI 0.9-7.0) when adding a previously developed CAD PGS to clinical risk factors (QRISK3). We used transferable loci as genetic instruments in trans-ancestry Mendelian randomisation and found evidence of an increased CAD risk for higher LDL-C and BMI, and for lower HDL-C in G&H, consistent with our findings for EUR samples. Conclusions: The genetic loci for CAD and its risk factors are largely transferable from EUR studies to British Pakistanis and Bangladeshis, whereas the transferability of PGSs varies greatly between traits. Our analyses suggest clinical utility for addition of PGS to existing clinical risk prediction tools for this population.

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