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BackgroundImmunocompromised patients may be at higher risk of mortality if hospitalised with COVID-19 compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death, and how this risk changed over the pandemic. MethodsWe included patients >=19yrs with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK. We defined immunocompromise as: immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination and co-morbidities. We used Bayesian logistic regression to explore mortality over time. FindingsBetween 17/01/2020 and 28/02/2022 we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. 29% (n=6,499) of immunocompromised and 21% (n=28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjOR 1.44, 95% CI 1.39-1.50, p<0.001). As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50-69yrs was 88% for men and 83% for women, and for those >80yrs was 99% for men, and 98% for women. ConclusionsImmunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses and monoclonal antibodies should be considered for this group. FundingNational Institute for Health Research; Medical Research Council; Chief Scientist Office, Scotland.
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ObjectiveTo examine if SARS-CoV-2 infections vary by vaccination status, if an individual had previously tested positive and by neighbourhood socioeconomic deprivation across the Delta and Omicron epidemic waves of SARS-CoV-2. DesignCohort study using electronic health records SettingCheshire and Merseyside, England (3rd June 2021 to 1st March 2022) Participants2.7M residents Main Outcome measureRegistered positive test for SARS-CoV-2 ResultsSocial inequalities in registered positive tests were dynamic during the study. Originally higher SARS-CoV-2 rates in the most socioeconomically deprived neighbourhoods changed to being higher in the least deprived neighbourhoods from the 1st September 2021. While the introduction of Omicron initially reset inequalities, they continued to be dynamic and inconsistent. Individuals who were fully vaccinated (two doses) were associated with fewer registered positive tests (e.g., between 1st September and 27th November 2021: (i) individuals engaged in testing - Hazards Ratio (HR) = 0.48, 95% Confidence Intervals (CIs) = 0.47-0.50; (ii) individuals engaged with healthcare - HR = 0.34, 95% CIs = 0.33-0.34). Individuals with a previous registered positive test were also less likely to have a registered positive test (e.g., between 1st September and 27th November 2021: (i) individuals engaged in testing - HR = 0.16, 95% CIs = 0.15-0.18; (ii) individuals engaged with healthcare - HR = 0.14, 95% CIs = 0.13-0.16). However, Omicron is disrupting these associations due to immune escape resulting in smaller effect sizes for both measures. ConclusionsChanging patterns of SARS-CoV-2 infections during the Delta and Omicron waves reveals a dynamic pandemic that continues to affect diverse communities in sometimes unexpected ways.
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BackgroundMortality rates of UK patients hospitalised with COVID-19 appeared to fall during the first wave. We quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital. MethodsThe International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK recruited a prospective cohort admitted to 247 acute UK hospitals with COVID-19 in the first wave (March to August 2020). Outcome was hospital mortality within 28 days of admission. We performed a three-way decomposition mediation analysis using natural effects models to explore associations between week of admission and hospital mortality adjusting for confounders (demographics, comorbidity, illness severity) and quantifying potential mediators (respiratory support and steroids). FindingsUnadjusted hospital mortality fell from 32.3% (95%CI 31.8, 32.7) in March/April to 16.4% (95%CI 15.0, 17.8) in June/July 2020. Reductions were seen in all ages, ethnicities, both sexes, and in comorbid and non-comorbid patients. After adjustment, there was a 19% reduction in the odds of mortality per 4 week period (OR 0.81, 95%CI 0.79, 0.83). 15.2% of this reduction was explained by greater disease severity and comorbidity earlier in the epidemic. The use of respiratory support changed with greater use of non-invasive ventilation (NIV). 22.2% (OR 0.94, 95%CI 0.94, 0.96) of the reduction in mortality was mediated by changes in respiratory support. InterpretationThe fall in hospital mortality in COVID-19 patients during the first wave in the UK was partly accounted for by changes in case mix and illness severity. A significant reduction was associated with differences in respiratory support and critical care use, which may partly reflect improved clinical decision making. The remaining improvement in mortality is not explained by these factors, and may relate to community behaviour on inoculum dose and hospital capacity strain. FundingNIHR & MRC Key points / Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSRisk factors for mortality in patients hospitalised with COVID-19 have been established. However there is little literature regarding how mortality is changing over time, and potential explanations for why this might be. Understanding changes in mortality rates over time will help policy makers identify evolving risk, strategies to manage this and broader decisions about public health interventions. Added value of this studyMortality in hospitalised patients at the beginning of the first wave was extremely high. Patients who were admitted to hospital in March and early April were significantly more unwell at presentation than patients who were admitted in later months. Mortality fell in all ages, ethnic groups, both sexes and in patients with and without comorbidity, over and above contributions from falling illness severity. After adjustment for these variables, a fifth of the fall in mortality was explained by changes in the use of respiratory support and steroid treatment, along with associated changes in clinical decision-making relating to supportive interventions. However, mortality was persistently high in patients who required invasive mechanical ventilation, and in those patients who received non-invasive ventilation outside of critical care. Implications of all the available evidenceThe observed reduction in hospital mortality was greater than expected based on the changes seen in both case mix and illness severity. Some of this fall can be explained by changes in respiratory care, including clinical learning. In addition, introduction of community policies including wearing of masks, social distancing, shielding of vulnerable patients and the UK lockdown potentially resulted in people being exposed to less virus. The decrease in mortality varied depending on the level of respiratory support received. Patients receiving invasive mechanical ventilation have persistently high mortality rates, albeit with a changing case-mix, and further research should target this group. Severe COVID-19 disease has primarily affected older people in the UK. Many of these people, but not all have significant frailty. It is essential to ensure that patients and their families remain at the centre of decision-making, and we continue with an individualised approach to their treatment and care.
