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      Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study

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          Summary

          Background

          Immunocompromised individuals are not optimally protected by COVID-19 vaccines and potentially require additional preventive interventions to mitigate the risk of severe COVID-19. We aimed to characterise and describe the risk of severe COVID-19 across immunocompromised groups as the pandemic began to transition to an endemic phase.

          Methods

          COVID-19-related hospitalisations, intensive care unit (ICU) admissions, and deaths (01/01/2022-31/12/2022) were compared among different groups of immunocompromised individuals vs the general population, using a retrospective cohort design and electronic health data from a random 25% sample of the English population aged ≥12 years (Registration number: ISRCTN53375662).

          Findings

          Overall, immunocompromised individuals accounted for 3.9% of the study population, but 22% (4585/20,910) of COVID-19 hospitalisations, 28% (125/440) of COVID-19 ICU admissions, and 24% (1145/4810) of COVID-19 deaths in 2022. Restricting to those vaccinated with ≥3 doses of COVID-19 vaccine (∼84% of immunocompromised and 51% of the general population), all immunocompromised groups remained at increased risk of severe COVID-19 outcomes, with adjusted incidence rate ratios (aIRR) for hospitalisation ranging from 1.3 to 13.1. At highest risk for COVID-19 hospitalisation were individuals with: solid organ transplant (aIRR 13.1, 95% confidence interval [95% CI] 11.2–15.3), moderate to severe primary immunodeficiency (aIRR 9.7, 95% CI 6.3–14.9), stem cell transplant (aIRR 11.0, 95% CI 6.8–17.6), and recent treatment for haematological malignancy (aIRR 10.6, 95% CI 9.5–11.9). Results were similar for COVID-19 ICU admissions and deaths.

          Interpretation

          Immunocompromised individuals continue to be impacted disproportionately by COVID-19 and have an urgent need for additional preventive measures beyond current vaccination programmes. These data can help determine the immunocompromised groups for which targeted prevention strategies may have the highest impact.

          Funding

          This study was funded by doi 10.13039/100004325, AstraZeneca UK; .

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          Most cited references41

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          Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

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            Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study

            Background The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. Methods We did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, we assessed disease severity and hospitalisations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021. Findings From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3·2%) of 63 in week 39 to 21 978 (97·9%) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2·4%] of 10 547 vs 121 [12·8%] of 948; adjusted odds ratio [aOR] 0·2, 95% CI 0·1–0·3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21%] of 204 vs 45 [40%] of 113; aOR 0·7, 95% CI 0·3–1·4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62·5%] of 793 vs 57 [23·4%] of 244; aOR 0·3, 95% CI 0·2–0·5), after controlling for factors associated with disease severity. Interpretation Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. Funding The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Fleming Fund.
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              Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant

              The emergence of the Omicron variant of SARS-CoV-2 is an urgent global health concern 1 . In this study, our statistical modelling suggests that Omicron has spread more rapidly than the Delta variant in several countries including South Africa. Cell culture experiments showed Omicron to be less fusogenic than Delta and than an ancestral strain of SARS-CoV-2. Although the spike (S) protein of Delta is efficiently cleaved into two subunits, which facilitates cell–cell fusion 2,3 , the Omicron S protein was less efficiently cleaved compared to the S proteins of Delta and ancestral SARS-CoV-2. Furthermore, in a hamster model, Omicron showed decreased lung infectivity and was less pathogenic compared to Delta and ancestral SARS-CoV-2. Our multiscale investigations reveal the virological characteristics of Omicron, including rapid growth in the human population, lower fusogenicity and attenuated pathogenicity.
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                Author and article information

                Contributors
                Journal
                Lancet Reg Health Eur
                Lancet Reg Health Eur
                The Lancet Regional Health - Europe
                Elsevier
                2666-7762
                13 October 2023
                December 2023
                13 October 2023
                : 35
                : 100747
                Affiliations
                [a ]Department of Respiratory Sciences, University of Leicester, Leicester, United Kingdom
                [b ]AstraZeneca UK Limited, BioPharmaceuticals Medical, Vaccines & Immunotherapies, Eastbrook House, First Floor, Shaftesbury Road, Cambridge, CB2 8DU, United Kingdom
                [c ]Evidera, The Ark, 201 Talgarth Road, London W6 8BJ, United Kingdom
                [d ]Data Analytics - Real World Evidence, Evidera, London, United Kingdom
                [e ]Vaccines and Immune Therapies, Global Market Access and Pricing, AstraZeneca R&D, 431 83 Mölndal, Sweden
                [f ]Nuffield Department of Medicine, University of Oxford, OUH Hospital NHS Trust, Oxford, United Kingdom
                [g ]Population Health and Genomics, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, DD1 9SY, Scotland, United Kingdom
                [h ]Medical and Payer Evidence Statistics, BioPharmaceuticals Medical, AstraZeneca, Cambridge, United Kingdom
                [i ]Evidera, Waltham, MA 02451, United States
                [j ]Integrated Solutions – Real World Evidence, Evidera, Stockholm, Sweden
                [k ]Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
                [l ]University Hospitals Birmingham, NHS Foundation Trust, Birmingham, United Kingdom
                [m ]Medical and Payer Evidence, BioPharmaceuticals Medical, AstraZeneca, Cambridge, United Kingdom
                [n ]P95, Leuven, Belgium
                [o ]AstraZeneca LP, 1800 Concord Pike, Wilmington, DE, 19850-5437, USA
                [p ]Medical Affairs, AstraZeneca UK Limited, BioPharmaceuticals Medical, Vaccines & Immunotherapies, Eastbrook House, First Floor, Shaftesbury Road, Cambridge, CB2 8DU, United Kingdom
                [q ]Medical Evidence, AstraZeneca UK Limited, BioPharmaceuticals Medical, Vaccines & Immunotherapies, Eastbrook House, First Floor, Shaftesbury Road, Cambridge, CB2 8DU, United Kingdom
                [r ]National Heart & Lung Institute, Imperial College London, United Kingdom
                Author notes
                []Corresponding author. j.quint@ 123456imperial.ac.uk
                Article
                S2666-7762(23)00166-7 100747
                10.1016/j.lanepe.2023.100747
                10730312
                38115964
                66ded2e5-be94-4a4c-bb74-e298c6e9ac18
                © 2023 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 10 July 2023
                : 15 September 2023
                : 21 September 2023
                Categories
                Articles

                covid-19,retrospective studies,immunocompromised,hospitalisation,icu admission,mortality,england,epidemiology

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