Changes in COVID-19-related mortality across key demographic and clinical subgroups in England from 2020 to 2022: a retrospective cohort study using the OpenSAFELY platform.

BACKGROUND: COVID-19 has been shown to differently affect various demographic and clinical population subgroups. We aimed to describe trends in absolute and relative COVID-19-related mortality risks across clinical and demographic population subgroups during successive SARS-CoV-2 pandemic waves. METHODS: We did a retrospective cohort study in England using the OpenSAFELY platform with the approval of National Health Service England, covering the first five SARS-CoV-2 pandemic waves (wave one [wild-type] from March 23 to May 30, 2020; wave two [alpha (B.1.1.7)] from Sept 7, 2020, to April 24, 2021; wave three [delta (B.1.617.2)] from May 28 to Dec 14, 2021; wave four [omicron (B.1.1.529)] from Dec 15, 2021, to April 29, 2022; and wave five [omicron] from June 24 to Aug 3, 2022). In each wave, we included people aged 18-110 years who were registered with a general practice on the first day of the wave and who had at least 3 months of continuous general practice registration up to this date. We estimated crude and sex-standardised and age-standardised wave-specific COVID-19-related death rates and relative risks of COVID-19-related death in population subgroups. FINDINGS: 18 895 870 adults were included in wave one, 19 014 720 in wave two, 18 932 050 in wave three, 19 097 970 in wave four, and 19 226 475 in wave five. Crude COVID-19-related death rates per 1000 person-years decreased from 4·48 deaths (95% CI 4·41-4·55) in wave one to 2·69 (2·66-2·72) in wave two, 0·64 (0·63-0·66) in wave three, 1·01 (0·99-1·03) in wave four, and 0·67 (0·64-0·71) in wave five. In wave one, the standardised COVID-19-related death rates were highest in people aged 80 years or older, people with chronic kidney disease stage 5 or 4, people receiving dialysis, people with dementia or learning disability, and people who had received a kidney transplant (ranging from 19·85 deaths per 1000 person-years to 44·41 deaths per 1000 person-years, compared with from 0·05 deaths per 1000 person-years to 15·93 deaths per 1000 person-years in other subgroups). In wave two compared with wave one, in a largely unvaccinated population, the decrease in COVID-19-related mortality was evenly distributed across population subgroups. In wave three compared with wave one, larger decreases in COVID-19-related death rates were seen in groups prioritised for primary SARS-CoV-2 vaccination, including people aged 80 years or older and people with neurological disease, learning disability, or severe mental illness (90-91% decrease). Conversely, smaller decreases in COVID-19-related death rates were observed in younger age groups, people who had received organ transplants, and people with chronic kidney disease, haematological malignancies, or immunosuppressive conditions (0-25% decrease). In wave four compared with wave one, the decrease in COVID-19-related death rates was smaller in groups with lower vaccination coverage (including younger age groups) and conditions associated with impaired vaccine response, including people who had received organ transplants and people with immunosuppressive conditions (26-61% decrease). INTERPRETATION: There was a substantial decrease in absolute COVID-19-related death rates over time in the overall population, but demographic and clinical relative risk profiles persisted and worsened for people with lower vaccination coverage or impaired immune response. Our findings provide an evidence base to inform UK public health policy for protecting these vulnerable population subgroups. FUNDING: UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.

Clinical and health inequality risk factors for non-COVID-related sepsis during the global COVID-19 pandemic: a national case-control and cohort study.

Background: Sepsis, characterised by significant morbidity and mortality, is intricately linked to socioeconomic disparities and pre-admission clinical histories. This study aspires to elucidate the association between non-COVID-19 related sepsis and health inequality risk factors amidst the pandemic in England, with a secondary focus on their association with 30-day sepsis mortality. Methods: With the approval of NHS England, we harnessed the OpenSAFELY platform to execute a cohort study and a 1:6 matched case-control study. A sepsis diagnosis was identified from the incident hospital admissions record using ICD-10 codes. This encompassed 248,767 cases with non-COVID-19 sepsis from a cohort of 22.0 million individuals spanning January 1, 2019, to June 31, 2022. Socioeconomic deprivation was gauged using the Index of Multiple Deprivation score, reflecting indicators like income, employment, and education. Hospitalisation-related sepsis diagnoses were categorised as community-acquired or hospital-acquired. Cases were matched to controls who had no recorded diagnosis of sepsis, based on age (stepwise), sex, and calendar month. The eligibility criteria for controls were established primarily on the absence of a recorded sepsis diagnosis. Associations between potential predictors and odds of developing non-COVID-19 sepsis underwent assessment through conditional logistic regression models, with multivariable regression determining odds ratios (ORs) for 30-day mortality. Findings: The study included 224,361 (10.2%) cases with non-COVID-19 sepsis and 1,346,166 matched controls. The most socioeconomic deprived quintile was associated with higher odds of developing non-COVID-19 sepsis than the least deprived quintile (crude OR 1.80 [95% CI 1.77-1.83]). Other risk factors (after adjusting comorbidities) such as learning disability (adjusted OR 3.53 [3.35-3.73]), chronic liver disease (adjusted OR 3.08 [2.97-3.19]), chronic kidney disease (stage 4: adjusted OR 2.62 [2.55-2.70], stage 5: adjusted OR 6.23 [5.81-6.69]), cancer, neurological disease, immunosuppressive conditions were also associated with developing non-COVID-19 sepsis. The incidence rate of non-COVID-19 sepsis decreased during the COVID-19 pandemic and rebounded to pre-pandemic levels (April 2021) after national lockdowns had been lifted. The 30-day mortality risk in cases with non-COVID-19 sepsis was higher for the most deprived quintile across all periods. Interpretation: Socioeconomic deprivation, comorbidity and learning disabilities were associated with an increased odds of developing non-COVID-19 related sepsis and 30-day mortality in England. This study highlights the need to improve the prevention of sepsis, including more precise targeting of antimicrobials to higher-risk patients. Funding: The UK Health Security Agency, Health Data Research UK, and National Institute for Health Research.

HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform.

BACKGROUND: Whether HIV infection is associated with risk of death due to COVID-19 is unclear. We aimed to investigate this association in a large-scale population-based study in England. METHODS: We did a retrospective cohort study. Working on behalf of NHS England, we used the OpenSAFELY platform to analyse routinely collected electronic primary care data linked to national death registrations. We included all adults (aged ≥18 years) alive and in follow-up on Feb 1, 2020, and with at least 1 year of continuous registration with a general practitioner before this date. People with a primary care record for HIV infection were compared with people without HIV. The outcome was COVID-19 death, defined as the presence of International Classification of Diseases 10 codes U07.1 or U07.2 anywhere on the death certificate. Cox regression models were used to estimate the association between HIV infection and COVID-19 death; they were initially adjusted for age and sex, then we added adjustment for index of multiple deprivation and ethnicity, and then for a broad range of comorbidities. Interaction terms were added to assess effect modification by age, sex, ethnicity, comorbidities, and calendar time. RESULTS: 17 282 905 adults were included, of whom 27 480 (0·16%) had HIV recorded. People living with HIV were more likely to be male, of Black ethnicity, and from a more deprived geographical area than the general population. 14 882 COVID-19 deaths occurred during the study period, with 25 among people with HIV. People living with HIV had higher risk of COVID-19 death than those without HIV after adjusting for age and sex: hazard ratio (HR) 2·90 (95% CI 1·96-4·30; p<0·0001). The association was attenuated, but risk remained high, after adjustment for deprivation, ethnicity, smoking and obesity: adjusted HR 2·59 (95% CI 1·74-3·84; p<0·0001). There was some evidence that the association was larger among people of Black ethnicity: HR 4·31 (95% CI 2·42-7·65) versus 1·84 (1·03-3·26) in non-Black individuals (p-interaction=0·044). INTERPRETATION: People with HIV in the UK seem to be at increased risk of COVID-19 mortality. Targeted policies should be considered to address this raised risk as the pandemic response evolves. FUNDING: Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, Health Data Research UK.