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Background: \ud The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.\ud \ud Methods: \ud This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status.\ud \ud Findings: \ud Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.\ud \ud Interpretation: \ud This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.\ud \ud Funding: \ud Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.

Hepatitis B virus (HBV) is a partially double stranded DNA virus that can integrate into host cell chromosomes as covalently closed circular DNA forms. HBV reactivation following hematopoietic stem cell transplantation in recipients with evidence of past HBV exposure, as well as exacerbation of a current HBV infection in HBV carrier recipients, secondary to chemotherapy and post-transplant immunosuppression that affect both humoral and cell-mediated control of HBV infection, are well documented in the literature. Management options include HBV-DNA screening and antiviral prophylaxis. Nucleos(t)ide analogues have been used at the start of chemotherapy and pretransplantation, with the course continuing for 6 months. However, depending on the serum HBV-DNA level, the antiviral agent might be given until a therapeutic end point is reached.

Department of Virology, Health Protection Agency Microbiology Services, Newcastle, UK Department of Haematology, Newcastle upon Tyne NHS Foundation Trust, Newcastle, UK Department of Microbiology, Newcastle upon Tyne NHS Foundation Trust, Newcastle, UK Antiviral Unit, Health Protection Agency Microbiology Services, Colindale, UK Department of Clinical Microbiology, St James’s Hospital, Dublin, Ireland

A 50-year-old Afro-Caribbean male with underlying hypertenion and chronic kidney disease stage 5 was found to be HIV-1 ntibody positive after annual screening for HIV in the renal unit. e had been expecting this result as his new female partner had een found to be HIV-1 infected having been admitted to hospial recently from the accident and emergency department with uberculosis. He had been on haemodialysis for the preceding years and was active on the national cadaveric kidney translant list, from which he was suspended pending control of his IV infection. His baseline HIV-1 RNA load was 92,400 copies/ml 5.0 log10) with a CD4 count of 251 cells/mm3 (19%). No antiretroiral resistance mutations were found on baseline HIV-1 drug esistance testing. The partner also had wild-type virus on baseine testing. He was booked in to the HIV clinic where he was o be started on combination antiretroviral therapy (cART) but efaulted his first clinic appointment and was seen 3 months after

Objective Vertical transmission of the hepatitis B virus (HBV) is the commonest mode of infection and can be prevented with immunoprophylaxis of the infant and antiviral therapy in the mother. Our aim was to review a cohort of subjects with HBV in pregnancy to determine the prevalence of active disease or high HBV-DNA levels that required treatment to prevent transmission, and to review the management of mothers and infants. Methods A retrospective case-note review was conducted of all the HBV-infected pregnant women and their infants who attended the Newcastle obstetric services from 2007 to 2011. Results There were 113 pregnancies in 81 women (median age 28 years; 15% hepatitis B e antigen (HBeAg) positive) during 2007–11. 71% of mothers were first diagnosed with HBV during pregnancy. The mothers were born in 28 different countries. 69% of mothers had an HBV-DNA level less than 2000 IU/mL and 13% had HBV-DNA levels greater than 1.0×10 7 IU/mL so would be eligible for antiviral therapy to prevent transmission to the infant. 9% had active eAg-positive HBV and 3% had active eAg-negative HBV requiring treatment. All infants born to HBeAg-positive mothers received hepatitis B immunoglobulin (HBIG) appropriately and 76% of infants received a full HBV vaccination course. One infant born to an HBeAg-negative mother was hepatitis B surface antigen positive 1 year post-delivery. Conclusions One in six women had active HBV requiring treatment or high HBV-DNA levels that would benefit from antiviral treatment to reduce the transmission risk. HBIG was administered appropriately but completion of the vaccination course was suboptimal.

The uptake of antenatal HIV testing in England and Scotland improved from 33% in 1998 to 92% in 2004 after implementing an opt-out policy. However, there is the potential for missing HIV seroconversion during pregnancy unless a further test is carried out between antenatal booking, which mostly occurs between 12-14 weeks, and delivery. We report a 32-year old Caucasian woman who developed a primary symptomatic HIV infection late in pregnancy. Unfortunately, despite antiretroviral treatment, caesarean section and formula feeding to reduce the risk of mother to child transmission (MCT), the baby was found to be infected by 12 weeks of age. Despite a 95% uptake rate at King's College Hospital, another HIV seroconversion during late pregnancy was detected after the partner was admitted with AIDS defining diagnoses. In the absence of national data on HIV seroconversion rates in pregnancy, further maternal HIV testing later in pregnancy, especially for women at-risk in an ethnically diverse area such as London, should be considered.

Individuals with past exposure to hepatitis B virus (HBV) may reactivate HBV following bone marrow transplantation. Alemtuzumab (CAMPATH)-based reduced intensity conditioning bone marrow transplantation has been associated with a high incidence of viral infections. Lamivudine prophylaxis for HBV should be instituted in this setting. The management of 240 CAMPATH-based reduced intensity conditioning bone marrow transplantation, carried out over an 8-year period at Kings College Hospital, was reviewed. Hepatitis B core total antibody (anti-HBc) testing identified recipients and donors with previous HBV exposure. Fifteen donor-recipient pairs were identified as being at risk of HBV reactivation. Eight recipients of anti-HBc negative donors were HBsAg negative, anti-HBc positive pre-transplantation. Five anti-HBc negative recipients received transplants from HBsAg negative, anti-HBc positive donors. Two HBV carrier recipients had one anti-HBc negative and one positive donor, respectively. Pre-transplant lamivudine prophylaxis was given to 8/10 (80%) anti-HBc positive recipients. Although HBsAg and HBV DNA were detected 4 months after bone marrow transplantation in one patient who did not receive prophylaxis, a good antiviral response was documented on starting lamivudine. The two HBV carrier recipients had stopped lamivudine at 8 and 31 months post-bone marrow transplantation, respectively, and died of liver failure with a sharp rise in HBV DNA levels. The five anti-HBc negative recipients with anti-HBc positive donors remained HBsAg and HBV DNA negative. Although lamivudine prophylaxis prevented HBV reactivation, it is unclear at what stage post-transplantation prophylaxis can be discontinued. Close monitoring of liver function tests (LFTs), HBsAg, and HBV DNA must be undertaken even after stopping antiviral prophylaxis.

Introduction Chronic HBV (cHBV) is a frequent cause of cirrhosis and liver cancer. Many infected individuals are unaware of their condition. Migrants from countries with high prevalence of cHBV, such as China and the Far East (seroprevalence 7–12%), are a high risk group for cHBV. Targeted HBV screening and vaccination is recommended by the AASLD1 and the European Liver Patients Association (ELPA)2 in high risk groups including subjects born in endemic areas. However, there are no current UK guidelines. Aim To apply AASLD and ELPA recommendations to British-Chinese community of North East (NE) England. Method Members of the NE Chinese community were invited to attend screening sessions at the Newcastle Chinese Healthy Living Centre [charity registration no. 1125227]. Dry blood spots were obtained by finger prick and tested for HBsAg and HBcAb (Abbott ARCHITECT). HBsAg positive individuals were advised to undergo confirmatory testing and be referred for specialist assessment. Results 575 subjects were screened in 10 sessions (mean age 49±17 years, 61% female). 53 (9%) were HBsAg positive (48% female) indicating cHBV. 10 of these reported being previously diagnosed with HBV, but were not under follow-up. The prevalence of HBsAg positivity was 7.5% when previously diagnosed individuals were excluded. 80 (14%) subjects had past infection with HBV (HBsAg negative, HBcAb positive). Individuals with past HBV were significantly older than HBsAg positive and HBsAg, HBcAb negative subjects (p Conclusion 1. Undiagnosed cHBV is common in the British-Chinese community of NE England, including subjects born in the UK. 2. A proportion had active cHBV requiring treatment. 3. If these results were applied to the entire UK British-Chinese population targeted screening should lead to approximately 32 250 newly diagnosed cases of cHBV. 4. These results provide evidence for a UK HBV screening and vaccination program for the British-Chinese community.

Introduction HBV is a common cause of chronic liver disease worldwide. Vertical transmission is the commonest mode of infection. Since 2000 antenatal HBV screening is offered to all pregnant women in the UK. The British Viral Hepatitis Group recommend treating mothers with an HBV DNA level of >10 7 IU/ml with antivirals in the 3rd trimester to reduce the transmission risk. Few studies have evaluated the epidemiology/management of pregnant patients with HBV in the UK. We reviewed the management of mothers with HBV attending our obstetric services. Methods Retrospective notes review of all HBV positive mothers who attended the obstetric service from January 07 to November 11. Data were collected on patient demographics, viral serology, HBV DNA and ALT levels and HBV management during their first pregnancy in the time period. Results 81 HBsAg positive mothers (median age 28, 18–44) had 113 pregnancies in the study period. 96% were referred to the viral hepatitis service; however 28% of women did not attend >1 appointment. The mothers were born in 28 countries, most commonly China (30%) followed by countries in Eastern Europe (17%), Africa (16%), South Asia (16%) and elsewhere (21%). 29% were known to have chronic HBV (cHBV). All mothers were tested for HBeAg/Ab status: 15% were HBeAg positive, 85% HBeAg negative and 79% anti-HBe positive. 85% had HBV DNA checked during the pregnancy. 9% had active HBeAg positive cHBV (HBV DNA >20 000 IU/ml, ALT >40), 3% had active HBeAg negative cHBV (HBV DNA >2000 and ALT >40), 9% were immunotolerant (HBeAg positive, ALT 10 7 IU/ml, but only two patients were treated with tenofovir in the 3rd trimester. Of the eight patients with active HBV, six were successfully treated post-partum with oral antivirals/PEG-Interferon and two became inactive. 20% of inactive carriers experienced a post-partum flare in ALT that settled spontaneously. Conclusion A high proportion of HBV infected mothers were born overseas; >1 in 6 had active cHBV or HBV DNA >10 7 IU/ml and were eligible for treatment to reduce the vertical transmission risk and/or prevent disease progression. All HBV infected mothers should be assessed for treatment and efforts to improve attendance at clinic appointments need to be intensified. Competing interests None declared.

Introduction Chronic HBV (cHBV) and HCV (cHCV) are frequent causes of cirrhosis and liver cancer. cHBV and cHCV are prevalent in subjects from South Asian countries and many infected individuals are unaware of their condition. A previous case finding pilot for HBV in the British–Chinese community of the NE of England found that 9% of subjects tested were HBsAg positive. 1 Targeted screening for HBV and HCV is recommended by the AASLD 2 and the European Liver Patients Association 3 in subjects born in endemic areas (HBsAg prevalence ≥2%). However, there are no current UK guidelines. Our aim was to apply AASLD recommendations to British South Asian community of NE of England. Methods Members of the NE South Asian community were invited to attend screening sessions at a Newcastle Mosque and the Sunderland Bangladeshi Community Centre. Dry blood spots were obtained by finger prick and tested for HBsAg, HBcAb (Abbott ARCHITECT®) and HCV antibody (Roche + confirmed by Biorad). HBsAg and/or HCV Ab positive individuals were advised to undergo confirmatory testing and be referred for specialist assessment. Results To date, 329 subjects were screened in four sessions (median age 39, range 6–83; 75% male). The screened subjects were most frequently born in Bangladesh (49%) followed by Pakistan (36%), the UK (14%) or other countries (6%). 1.8% of subjects were HBsAg positive indicating cHBV. 2.8% of subjects had past infection with HBV (HBsAg negative, HBcAb positive). 1% of subjects were HCV Ab positive (all born in Pakistan). The prevalence of cHBV was 3% for individuals born in Pakistan and 1.5% for those born in Bangladesh. 3% of individuals born in Pakistan were HCV Ab positive. Only 4% of subjects reported previous vaccination against HBV. Conclusion Undiagnosed cHBV is prevalent in the South Asian community of NE England, although the prevalence was lower than in the British–Chinese community. These results provide evidence for a targeted case finding programme for HBV and HCV in subjects born in South Asia. Funding This study was supported by a Gilead UK and Ireland Fellowship and Livernorth. Competing interests None declared. References 1. McPherson S , et al. Gut 2011; 60 (Supp 2):A25. 2. Lok A , McMahon B. Hepatology 2009; 50 :1–36. 3. Piorkowsky N . J Hepatol 2009; 51 :1068–73.

Abstract 4617 We report 3 patients who developed Haemophagocytic Lymphohistiocytosis (HLH) following treatment with Fludarabine/Cyclophosphamide (FC) chemotherapy for Chronic Lymphocytic Leukaemia (CLL). Acquired (secondary) HLH is more frequent than primary (familial) HLH and usually described in patients with an underlying immune disorder. Acquired HLH in association with haematological malignancies is well recognised. The most commonly reported associations in adults are NK/T and peripheral T cell lymphomas. There is only one previous published case report of HLH in association with CLL as a direct trigger for development of HLH where the patient developed HLH one month after FC therapy and died in spite of treatment with the HLH 2004 protocol. Our 3 patients were diagnosed with HLH using standard diagnostic criteria, fulfilling at least 5 out of 8 clinical/laboratory criteria (Table 1). There was no evidence of haemophagocytosis in the bone marrow of any of these patients prior to treatment with FC. Two patients are still alive while the other died one month after diagnosis.Table 1Patient 1Patient 2Patient 3Fever+++Splenomegaly (cm)181719Haemoglobin (g/dl)10.39.07.3Platelets (× 109/l)116319Neutrophils (× 109/l)0.81.020.6Haemophagocytosis in bone marrow+++Ferritin (ug/l)165009342>100000Triglycerides (0.5–1.7 mmol/l)1.7 mmol/l1.9 mmol/l1.8 mmo/lFibrinogen level(2.1–4.8 g/l)0.6 g/l2.0 g/l1.0 g/lDecreased/absent NK cell activityNot assessedNot assessedNot assessedSoluble CD25Not assessedNot assessedNot assessed Each had been treated with FC before they developed HLH and 2 of them had received previous treatment with chlorambucil. All 3 patients were extensively investigated for infective causes that may be associated with HLH. Multiple blood, urine and sputum cultures were negative for bacteria, fungi, mycobacteria and parasites. Polymerase chain reaction (PCR) studies for cytomegalovirus, Epstein Barr virus, herpes simplex virus, human herpes virus-6 and parvovirus B19 were all negative initially in all 3 patients. Patient 2 developed immunosuppression related HHV-6 reactivation while he was undergoing treatment with HLH 2004. This responded to brief treatment with Foscarnet. All 3 patients were treated with empirical intravenous antibiotics for neutropenic sepsis and subsequently administered antifungal therapy due to prolonged fever not responding to antibiotics. All had whole body Computerised Tomography (CT) scans looking for any evidence of infection. CT scans in each case showed splenomegaly and minor adenopathy in the abdomen and chest with no evidence of infection. Bone marrow biopsies from all 3 patients showed appearances of haemophagocytosis but no significant residual infiltration with CLL. The time interval from treatment with FC to the development of HLH ranged from 1 month to 6 months (Table 2). Patient 1 died 4 weeks following the diagnosis of HLH in spite of treatment according to HLH 2004. The remaining 2 patients are still alive and undergoing treatment as per HLH 2004. Patient 2 has been worked up for allogenic bone marrow transplant (alloBMT) as part of HLH 2004. The other patient is being treated with chemotherapy alone due to age and other co morbidity factors precluding consideration for alloBMT.Table 2:Patient 1Patient 2Patient 3Age655774SexmalemalefemaleDate of first diagnosis of CLL09/05/200931/07/200605/06/2001Previous treatmentChlorambucilNoneChlorambucilTime of treatment with FC15/09/2009 To 28/06/201003/01/2009 to 09/10/2009 and 04/04/201104/03/2010 To 10/11/2010Number of FC cycles88 and 1(FC +Rituximab)6Date of diagnosis of HLH05/01/201115/05/201106/05/2011Current statusDied on 05/02/2011Undergoing treatment with HLH2004 and awaiting alloBMTUndergoing treatment with HLH2004 To our knowledge, this is the first case series of CLL patients who developed HLH in direct association with FC treatment without evidence of an underlying infective aetiology. Therefore in CLL patients presenting with cytopenias and fever, HLH should be considered early and diagnostic tests performed. This complication of treated CLL may be more common with FC than treatment with Chlorambucil alone, with which it had not previously been reported. Disclosures: No relevant conflicts of interest to declare.

Introduction Chronic hepatitis B (HBV) is highly prevalent in China and the Far East (>8% seroprevalence). AASLD guidelines1 recommend HBV screening and vaccination in subjects born in high (>8%) or intermediate (2–7%) endemic areas. However, there are no current UK guidelines. The study aim was to apply AASLD recommendations locally to the community with the highest endemicity – British Chinese (estimated population 430 000). Methods Members of the NE Chinese community were invited to attend screening sessions at the Newcastle Chinese Healthy Living Centre. Dry blood spots were obtained by finger prick and tested for HBsAg and HBcAb (Abbott ARCHITECT). HBsAg positive individuals were advised to undergo confirmatory testing and be referred for specialist assessment. Results 315 subjects were screened (mean age 52±18 years, 63% female). 31 (10%) were HBsAg positive (48% female) indicating chronic HBV. Of these, 7 reported being previously diagnosed with HBV, but were not under follow-up. When previously diagnosed individuals were excluded the prevalence of HBsAg positivity was 8%. 50 (16%) subjects were HBsAg negative and HBcAb positive indicating past HBV infection. HBsAg positive individuals were significantly younger than HBcAb and negative subjects (44±12 vs 59±15 vs 52±19 years, p Conclusion (1) Undiagnosed chronic Hepatitis B is highly prevalent in British-Chinese in NE England, including subjects born in the UK. (2) The frequency of previous HBV vaccination was low in this high risk group. (3) These results provide evidence for a UK HBV screening and vaccination program for the British Chinese community, which is the largest in Europe and is the fastest growing non-European ethnic group in the UK.

months. Out of 4 patients with HBV reactivation, 2 patients were treated with entecavir because they showed persistent increase in HBVDNA load. In the remaining 2 patients, HBVDNA level indicated transient elevations, and then decreased below the lower limit for quantification during close follow-up. None of 4 patients with HBV reactivation presented de novo hepatitis. Conclusions: In the patients with lymphoma or multiple myeloma, incidence of HBV reactivation was 6.8%, when anti-HBc were present prior to chemotherapy. Because patients with anti-HBc might be at high risk of HBV reactivation, they should be monitored closely for HBV-DNA levels during and after rituximab and steroid-containing treatment.