Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant.

BACKGROUND: A rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease caused by the omicron and delta (B.1.617.2) variants in England. Vaccine effectiveness was calculated after primary immunization with two doses of BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine and after a booster dose of BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273. RESULTS: Between November 27, 2021, and January 12, 2022, a total of 886,774 eligible persons infected with the omicron variant, 204,154 eligible persons infected with the delta variant, and 1,572,621 eligible test-negative controls were identified. At all time points investigated and for all combinations of primary course and booster vaccines, vaccine effectiveness against symptomatic disease was higher for the delta variant than for the omicron variant. No effect against the omicron variant was noted from 20 weeks after two ChAdOx1 nCoV-19 doses, whereas vaccine effectiveness after two BNT162b2 doses was 65.5% (95% confidence interval [CI], 63.9 to 67.0) at 2 to 4 weeks, dropping to 8.8% (95% CI, 7.0 to 10.5) at 25 or more weeks. Among ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased to 62.4% (95% CI, 61.8 to 63.0) at 2 to 4 weeks after a BNT162b2 booster before decreasing to 39.6% (95% CI, 38.0 to 41.1) at 10 or more weeks. Among BNT162b2 primary course recipients, vaccine effectiveness increased to 67.2% (95% CI, 66.5 to 67.8) at 2 to 4 weeks after a BNT162b2 booster before declining to 45.7% (95% CI, 44.7 to 46.7) at 10 or more weeks. Vaccine effectiveness after a ChAdOx1 nCoV-19 primary course increased to 70.1% (95% CI, 69.5 to 70.7) at 2 to 4 weeks after an mRNA-1273 booster and decreased to 60.9% (95% CI, 59.7 to 62.1) at 5 to 9 weeks. After a BNT162b2 primary course, the mRNA-1273 booster increased vaccine effectiveness to 73.9% (95% CI, 73.1 to 74.6) at 2 to 4 weeks; vaccine effectiveness fell to 64.4% (95% CI, 62.6 to 66.1) at 5 to 9 weeks. CONCLUSIONS: Primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant. A BNT162b2 or mRNA-1273 booster after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, but that protection waned over time. (Funded by the U.K. Health Security Agency.).

Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study.

BACKGROUND: The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort. METHODS: Individual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta (ie, the relative risk in unvaccinated cases). FINDINGS: The adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0·56 (95% CI 0·54-0·58); for hospital admission and death, HR estimates were 0·41 (0·39-0·43) and 0·31 (0·26-0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 (0·85-1·42) in those younger than 10 years, decreasing to 0·25 (0·21-0·30) in 60-69-year-olds, and then increasing to 0·47 (0·40-0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated (HR 0·47 [0·32-0·68]) and unvaccinated (0·18 [0·06-0·57]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR 0·96 [0·88-1·04]); however, for unvaccinated cases, past infection gave moderate protection (HR 0·55 [0·48-0·63]). Omicron versus delta HR estimates were lower for hospital admission (0·30 [0·28-0·32]) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases (HR for hospital admission 8-11 weeks post-booster vs unvaccinated: 0·22 [0·20-0·24]), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2. INTERPRETATION: The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections. FUNDING: Medical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research, Community Jameel, and Engineering and Physical Sciences Research Council.

Patient satisfaction with HIV care service in Spain: results from a cross-sectional patient survey.

Understanding patient satisfaction with healthcare services can help identify patients' unmet needs and increase treatment adherence. This study aimed to evaluate the satisfaction of people living with HIV with overall HIV care service in Navarra, Spain, using a cross-sectional survey. The survey included a patient-reported experience measure (PREMs) consisting of five statements, and participants were also asked to rate the overall care they receive from the HIV service. Chi-square tests were used to detect differences between groups for statements and Kruskal-Wallis rank test was used to detect differences in ranking of the HIV service. The 395 participants gave the HIV service a mean score of 9.3 points out of 10 (standard deviation 1.1). Only 15 (4%) gave a score of under 8 out of 10, and adherence to antiretroviral therapy was associated with higher ranking of the service. Agreement for all five statements ranged from 80% to 96%. Those without stable housing, with mental health problems, and unemployed felt less supported to manage their HIV. These results highlight the need to regularly assess patient satisfaction with the HIV care and that care should account for social and economic factors that could influence health.

Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29-3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.

Long-Term Health-Related Quality of Life in Non-Hospitalized Coronavirus Disease 2019 (COVID-19) Cases With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in England: Longitudinal Analysis and Cross-Sectional Comparison With Controls.

BACKGROUND: We aimed to quantify the unknown losses in health-related quality of life of coronavirus disease 2019 (COVID-19) cases using quality-adjusted lifedays (QALDs) and the recommended EQ-5D instrument in England. METHODS: Prospective cohort study of nonhospitalized, polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2-positive (SARS-CoV-2-positive) cases aged 12-85 years and followed up for 6 months from 1 December 2020, with cross-sectional comparison to SARS-CoV-2-negative controls. Main outcomes were QALD losses; physical symptoms; and COVID-19-related private expenditures. We analyzed results using multivariable regressions with post hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. RESULTS: Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on nonprescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95% confidence interval [CI]: 9.7, 17.7) QALDs, whereas those reporting symptoms at month 6 lost 32.9 (95% CI: 24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in the England. CONCLUSIONS: One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms.

COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) deaths are rare in children and young people (CYP). The high rates of asymptomatic and mild infections complicate assessment of cause of death in CYP. We assessed the cause of death in all CYP with a positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test since the start of the pandemic in England. METHODS AND FINDINGS: CYP aged <20 years who died within 100 days of laboratory-confirmed SARS-CoV-2 infection between 01 March 2020 and 31 December 2021 in England were followed up in detail, using national databases, surveillance questionnaires, post-mortem reports, and clinician interviews. There were 185 deaths during the 22-month follow-up and 81 (43.8%) were due to COVID-19. Compared to non-COVID-19 deaths in CYP with a positive SARS-CoV-2 test, death due to COVID-19 was independently associated with older age (aOR 1.06 95% confidence interval (CI) 1.01 to 1.11, p = 0.02) and underlying comorbidities (aOR 2.52 95% CI 1.27 to 5.01, p = 0.008), after adjusting for age, sex, ethnicity group, and underlying conditions, with a shorter interval between SARS-CoV-2 testing and death. Half the COVID-19 deaths (41/81, 50.6%) occurred within 7 days of confirmation of SARS-CoV-2 infection and 91% (74/81) within 30 days. Of the COVID-19 deaths, 61 (75.3%) had an underlying condition, especially severe neurodisability (n = 27) and immunocompromising conditions (n = 12). Over the 22-month surveillance period, SARS-CoV-2 was responsible for 1.2% (81/6,790) of all deaths in CYP aged <20 years, with an infection fatality rate of 0.70/100,000 SARS-CoV-2 infections in this age group estimated through real-time, nowcasting modelling, and a mortality rate of 0.61/100,000. Limitations include possible under-ascertainment of deaths in CYP who were not tested for SARS-CoV-2 and lack of direct access to clinical data for hospitalised CYP. CONCLUSIONS: COVID-19 deaths remain extremely rare in CYP, with most fatalities occurring within 30 days of infection and in children with specific underlying conditions.

SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN).

BACKGROUND: Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection. METHODS: A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2-4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts. FINDINGS: From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13-0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days. INTERPRETATION: A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. FUNDING: Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments.

COVID-19 mortality among people with diagnosed HIV compared to those without during the first wave of the COVID-19 pandemic in England.

OBJECTIVES: We describe COVID-19 mortality among people with and without HIV during the first wave of the pandemic in England. METHODS: National surveillance data on adults (aged ≥ 15 years) with diagnosed HIV resident in England were linked to national COVID-19 mortality surveillance data (2 March 2020-16 June 2020); HIV clinicians verified linked cases and provided information on the circumstances of death. We present COVID-19 mortality rates by HIV status, using negative binomial regression to assess the association between HIV and mortality, adjusting for gender, age and ethnicity. RESULTS: Overall, 99 people with HIV, including 61 of black ethnicity, died of/with COVID-19 (107/100 000) compared with 49 483 people without HIV (109/100 000). Compared to people without HIV, higher COVID-19 mortality rates were observed in people with HIV of black (188 vs. 122/100 000) and Asian (131 vs. 77.0/100 000) ethnicity, and in both younger (15-59 years: 58.3 vs. 10.2/100 000) and older (≥ 60 years: 434 vs. 355/100 000) people. After adjustment for demographic factors, people with HIV had a higher COVID-19 mortality risk than those without (2.18; 95% CI: 1.76-2.70). Most people with HIV who died of/with COVID-19 had suppressed HIV viraemia (91%) and at least one comorbidity reported to be associated with poor COVID-19 outcomes (87%). CONCLUSIONS: In the first wave of the pandemic in England, COVID-19 mortality among people with HIV was low, but was higher than in those without HIV, after controlling for demographic factors. This supports the strategy of prioritizing COVID-19 vaccination for people with HIV and strongly encouraging its uptake, especially in those of black and Asian ethnicity.

Assessment of mortality and hospital admissions associated with confirmed infection with SARS-CoV-2 Alpha variant: a matched cohort and time-to-event analysis, England, October to December 2020.

BackgroundThe emergence of the SARS-CoV-2 Alpha variant in England coincided with a rapid increase in the number of PCR-confirmed COVID-19 cases in areas where the variant was concentrated.AimOur aim was to assess whether infection with Alpha was associated with more severe clinical outcomes than the wild type.MethodsLaboratory-confirmed infections with genomically sequenced SARS-CoV-2 Alpha and wild type between October and December 2020 were linked to routine healthcare and surveillance datasets. We conducted two statistical analyses to compare the risk of hospital admission and death within 28 days of testing between Alpha and wild-type infections: a matched cohort study and an adjusted Cox proportional hazards model. We assessed differences in disease severity by comparing hospital admission and mortality, including length of hospitalisation and time to death.ResultsOf 63,609 COVID-19 cases sequenced in England between October and December 2020, 6,038 had the Alpha variant. In the matched cohort analysis, we matched 2,821 cases with Alpha to 2,821 to cases with wild type. In the time-to-event analysis, we observed a 34% increased risk in hospitalisation associated with Alpha compared with wild type, but no significant difference in the risk of mortality.ConclusionWe found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increased infection severity associated with the Alpha variant. Rapid assessments of the relative morbidity in terms of clinical outcomes and mortality associated with emerging SARS-CoV-2 variants compared with dominant variants are required to assess overall impact of SARS-CoV-2 mutations.

On the Sensitivity and Specificity of Postmortem Upper Respiratory Tract Testing for SARS-CoV-2.

BACKGROUND: Postmortem testing can improve our understanding of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) if sufficiently sensitive and specific. METHODS: We investigated the postmortem sensitivity and specificity of reverse transcriptase polymerase chain reaction (PCR) testing on upper respiratory swabs using a dataset of everyone tested for SARS-CoV-2 before and after death in England, 1 March to 29 October 2020. We analyzed sensitivity in those with a positive test before death by time to postmortem test. We developed a multivariate model and conducted time-to-negativity survival analysis. For specificity, we analyzed those with a negative test in the week before death. RESULTS: Postmortem testing within a week after death had a sensitivity of 96.8% if the person had tested positive within a week before death. There was no effect of age, sex, or specimen type on sensitivity, but individuals with coronavirus disease 2019 (COVID-19)-related codes on their death certificate were 5.65 times more likely to test positive after death (95% confidence interval, 2.31-13.9). Specificity was 94.2%, increasing to 97.5% in individuals without COVID-19 on the death certificate. CONCLUSION: Postmortem testing has high sensitivity (96.8%) and specificity (94.2%) if performed within a week after death and could be a useful diagnostic tool.

Epidemiology of Confirmed COVID-19 Deaths in Adults, England, March-December 2020.

Of the 58,186 coronavirus deaths among adults in England during March-December 2020, 77% occurred in hospitals, 93% were in patients >60 years, and 91% occurred within 28 days of positive specimen. Cumulative mortality rates were highest among persons of Black, Asian, other, or mixed ethnicities and in socioeconomically deprived areas.

Acceptability and usability of HIV self-tests in two European countries: findings from surveys of clients at non-governmental organisations in Lithuania and Italy.

BACKGROUND: Uptake of HIV self-tests (HIVST) remains low in Europe. We conducted two separate surveys to understand facilitators and barriers to the use of HIVST in two European countries, as part of the EU INTEGRATE Joint Action. In both countries, HIV has been legal since 2016. In Lithuania, where HIVST sales have been low, the survey primarily assessed acceptability whilst in Italy, with better HIVST uptake, usability was the focus. METHODS: Participants were recruited through community HIV testing sites, and in Lithuania also through social media. In Lithuania, participants self-completed a survey on their testing history, and attitudes toward and experiences with self-testing. In Italy participants performed an HIVST (Mylan Autotest) while being observed by a community health worker (CHW). Both participants and CHW completed a self-administered survey evaluating the experience of the participant. RESULTS: In Lithuania, awareness of HIV self-testing (75%) was high among the 138 people who completed the survey. Privacy and confidentiality (70%) was the most common reason to use an HIVST whilst cost was reported as the main barrier by 60%, only 15% were willing to pay the current price. Almost half (42%) were concerned about doing the test incorrectly and 36% preferred that a trained person could discuss their result. Purchasing HIVST at a pharmacy (70%) or online (61%) was favoured and 68% would opt to simultaneously test for other infections. In Italy, 28 people who had never used an HIVST before were observed using one. 43% found the test easy to use but CHWs reported that 36% of participants failed at least one step. The quick result (68%) was the most common reason to use one again, yet the main concerns were the lack of counselling (50%) and reading result alone (32%). CONCLUSIONS: HIVST are acceptable and usable, however cost is a major barrier. Local and national strategies are needed to increase awareness of and access to HIVST and target HIVST campaigns toward key risk groups such as MSM. Meanwhile, steps can be taken to improve testing instructions and support for self-testers. Offering multiplex testing for other infections would also likely increase uptake.

Quality of life in people living with HIV in Romania and Spain.

BACKGROUND: Health-related quality of life (HRQoL) is a crucial component in assessing and addressing the unmet needs of people, especially those with chronic illnesses such as HIV. The aim of the study was to examine and compare the health-related quality of life of people living with HIV in Romania and Spain, compared to the general populations of each country. METHODS: A cross-sectional survey was conducted among adults (≥ 18 years) attending for HIV care in Romania and Spain from October 2019 to March 2020. The survey included two validated HRQoL instruments: a generic instrument, EQ-5D-5L, and an HIV-specific instrument, PozQoL, and questions on socio-demographics, HIV-related characteristics, physical and mental health conditions, and substance use. Multivariable linear regression was used to determine factors associated with HRQoL. RESULTS: 570 people living with HIV responded (170 in Romania and 400 in Spain). The median age was 31 (18-67) in Romania and 52 (19-83) in Spain. Anxiety/depression symptoms were frequently reported by people with HIV (Romania: 50% vs 30% in the Romanian population; Spain: 38% vs 15% in Spanish population). Spain reported higher mean EQ-5Dutility scores than Romania (0.88 and 0.85, respectively) but identical PozQoL scores (3.5, on a scale of 0-5). In both countries, health concerns were highlighted as a key issue for people with HIV. In multivariable analysis, two factors were consistently associated with worse HRQoL in people with HIV: bad or very bad self-rated health status and presence of a mental health condition. In Romania, being gay/bisexual and being disabled/unemployed were associated with worse HRQoL. Whereas in Spain, older age and financial insecurity were significant predictors. CONCLUSIONS: Our results indicated a good HRQoL for people living with HIV in Romania and Spain; however, worse HRQoL profiles were characterized by health concerns, poor self-rated health status, and the presence of mental health conditions. This study highlights the importance of monitoring HRQoL in people living with HIV due to the chronic nature of the disease. In this highly-treatment experienced group, disparities were found, particularly highlighting mental health as an area which needs more attention to improve the well-being of people living with HIV.

Surge in SARS-CoV-2 transmission in school-aged children and household contacts, England, August to October 2021.

Easing of COVID-19 restrictions in England in the summer of 2021 was followed by a sharp rise in cases among school-aged children. Weekly rates of SARS-CoV-2 infection in primary and secondary school children reached 733.3 and 1,664.7/100,000 population, respectively, by week 39 2021. A surge in household clusters with school-aged index cases was noted at the start of the school term, with secondary cases predominantly in children aged 5-15 years and adults aged 30-49 years.

Estimated number of deaths directly averted in people 60 years and older as a result of COVID-19 vaccination in the WHO European Region, December 2020 to November 2021.

Since December 2019, over 1.5 million SARS-CoV-2-related fatalities have been recorded in the World Health Organization European Region - 90.2% in people ≥ 60 years. We calculated lives saved in this age group by COVID-19 vaccination in 33 countries from December 2020 to November 2021, using weekly reported deaths and vaccination coverage. We estimated that vaccination averted 469,186 deaths (51% of 911,302 expected deaths; sensitivity range: 129,851-733,744; 23-62%). Impact by country ranged 6-93%, largest when implementation was early.

Impact of TB on the survival of people living with HIV infection in England, Wales and Northern Ireland.

INTRODUCTION: The impact of TB disease on survival in people living with HIV in high resource settings is not well documented in the antiretroviral treatment (ART) era. We calculated TB incidence rates and compared the mortality of persons with and without HIV-TB in a UK HIV cohort in the post-ART era, to determine the impact of HIV-TB on survival in the UK. METHODS: We linked the national cohort of persons (aged ≥15 years) diagnosed with HIV between 2000 and 2008 in England, Wales and Northern Ireland with the national TB register and deaths from the Office of National Statistics. We compared all-cause and AIDS-specific mortality in patients with and without TB by estimating HRs using Cox regression modelling allowing for potential predictors. RESULTS: Overall, 3188 (7.2%) individuals developed TB infection among a cohort of 44 050 HIV-diagnosed persons and 149 663 person-years. The cumulative TB incidence rate was 2.13 per 100 person-years with a spike within the first 6 months after HIV diagnosis. TB coinfected patients comprised 18% of the 1880 deaths during follow-up and 79% of deaths (n=967) in the year following HIV diagnosis. TB coinfection (HR 4.77, 95% CI 4.11 to 5.54) was significantly associated with increased all-cause mortality. Analysis of AIDS-related survival showed similar results. DISCUSSION: The unexpected high mortality in patients with HIV-TB in a population with good healthcare access and ART availability highlights the importance of improving active and latent TB case-finding among patients with HIV, and HIV-testing among patients with TB, to ensure appropriate and prompt treatment initiation for both diseases.

Temporal changes to adult case fatality risk of COVID-19 after vaccination in England between May 2020 and February 2022: a national surveillance study.

OBJECTIVES: Risk of death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has fallen during the pandemic, largely due to immunity from vaccination. In England, the timing and extent of this reduction varied due to staggered eligibility during the primary vaccination campaign, based on age and clinical risk group. Duration of protection is less well understood. Our objective was to estimate the case fatality risk (CFR) by vaccination status and time since last dose during a period of widespread community testing, to better understand the impact of coronavirus disease 2019 (COVID-19) vaccination and duration of protection. DESIGN: SARS-CoV-2 cases diagnosed between May 2020 and February 2022 were linked to vaccine records from the National Immunisation Management System. CFR was calculated as the proportion of cases that died of COVID-19 per the death certificate, aggregated by week of specimen and stratified by 10-year age band and vaccination status. SETTING: England, UK. PARTICIPANTS: A total of 10,616,148 SARS-CoV-2 cases, aged ≥18 years, recorded by England's laboratory reporting system. MAIN OUTCOME MEASURES: Case fatality risk of COVID-19, stratified by age band and vaccination status. RESULTS: Overall, a reduction in CFR was observed for all age bands, with a clear temporal link to when the age group became eligible for primary vaccination and then the first booster. CFR increased with age (0.3% 50-59 years; 1.2% 60-69; 4.7% 70-79; 16.3% 80+) and was highest in the unvaccinated - albeit a reduction was observed over time. The highest CFR was seen in the unvaccinated 80+ group prior to vaccination rollout (30.6%). CFR was consistently lowest in vaccinated populations within 6 months of last dose, yet increased after over 6 months elapsed since last dose, across all age bands. CONCLUSIONS: COVID-19 CFR reduced after vaccination, with the lowest CFR seen across all age bands when vaccinated up to 6 months prior to specimen date. This provides some evidence for continued booster doses in older age groups.

HIV-related Stigma and Discrimination in Health Care and Health-related Quality of Life among People Living with HIV in England and Wales: A Latent Class Analysis.

Though life expectancy of people living with HIV (PLHIV) is now comparable to that of HIV-negative persons, their health-related quality of life (HRQoL) lags behind. Lower HRQoL among PLHIV may vary meaningfully, shaped in part by social factors, including stigma. Using data from Positive Voices, a national cross-sectional probability survey of adults ≥ 18 years living with HIV and accessing HIV care services in England and Wales (N = 4,422), we conducted latent class analysis on responses to a HRQoL measure (problems with mobility, usual activities, self-care, pain/discomfort, anxiety/depression) to identify HRQoL patterns, followed by multinomial logistic regression to examine relationships between HRQoL classes and a 4-item measure of HIV-related stigma and discrimination in health care. Four classes emerged: All Problems (18% prevalence); Pain and Distress (18%); Pain and Mobility (9%); No Problems (55%). Scale scores of HIV-related stigma and discrimination in health care were positively, significantly associated with membership in the All Problems (adjusted odds ratio [aOR] = 2.05; 95% confidence interval [CI] = 1.85, 2.28), Pain and Distress (aOR = 1.56; CI = 1.41, 1.73), and Pain and Mobility classes (aOR = 1.33; CI = 1.16, 1.52) compared to the No Problems class. A similar trend was observed for individual stigma and discrimination items. HRQoL among PLHIV in England and Wales varies and may be underpinned or exacerbated by HIV-related stigma and discrimination in health care. Ensuring stigma-mitigation interventions reach all health care systems/providers and emotional support services reach all PLHIV may improve HRQoL for PLHIV.

Vaccine effectiveness against hospitalisation estimated using a test-negative case-control study design, and comparative odds of hospital admission and severe outcomes with COVID-19 sub-lineages BQ.1, CH.1.1. and XBB.1.5 in England.

Background: Since the first emergence of Omicron BA.1 in England in November 2021, numerous sub-lineages have evolved. In September 2022, BA.5 dominated. The prevalence of BQ.1 increased from October, while the prevalence of CH.1.1 and XBB.1.5 increased from December 2022 and January 2023, respectively. Little is known about the effectiveness of the vaccines against hospitalisation with these sub-lineages, nor the relative severity, so we here used national-level electronic health records from England to estimate vaccine effectiveness and variant severity. Methods: The study period for tests contributing to all analyses was from 5th December 2022 to 2nd April 2023, when the variants of interest were co-circulating. A test-negative case-control study was used to estimate the incremental effectiveness of the bivalent BA.1 booster vaccines against hospitalisation, relative to those with waned immunity where the last dose was at least 6 months prior. The odds of hospital admission for those testing PCR positive on the day of an attendance to accident and emergency departments and the odds of intensive care unit admission or death amongst COVID-19 admissions were compared between variants. Additionally, a Cox proportional hazards survival regression was used to investigate length of stay amongst hospitalised cases by variant. Findings: Our vaccine effectiveness study included 191,229 eligible tests with 1647 BQ.1 cases, 877 CH.1.1 cases, 1357 XBB.1.5 cases and 187,348 test negative controls. There was no difference in incremental vaccine effectiveness against hospitalisation with BQ.1, CH.1.1 or XBB.1.5, nor was there a difference in the severity of these variants. Effectiveness against hospitalisation was 48.0% (95% C.I.; 38.5-56.0%), 29.7% (95% C.I.; 7.5-46.6%) and 52.7% (95% C.I.; 24.6-70.4%) against BQ.1, CH.1.1 and XBB.1.5, respectively, at 5-9 weeks post booster vaccination. Compared to BQ.1, the odds of hospital admission were 0.87 (95% C.I.; 0.77-0.99) and 0.88 (95% C.I.; 0.75-1.02) for CH.1.1 and XBB.1.5 cases attending accident and emergency departments, respectively. There was no significant difference in the odds of admission to intensive care units or death for those with CH.1.1 (OR 0.96, 95% C.I.; 0.71-1.30) or XBB.1.5 (OR 0.67, 95% C.I.; 0.44-1.02) compared to BQ.1. There was also no significant difference in the length of hospital stay by variant. Interpretation: Together, these results provide reassuring evidence that the bivalent BA.1 booster vaccines provide similar protection against hospitalisation with BQ.1, CH.1.1 and XBB.1.5, and that the emergent CH.1.1 and XBB.1.5 sub-lineages do not cause more severe disease than BQ.1. Funding: None.