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Meta-Analysis
. 2024 Mar;88(3):106110.
doi: 10.1016/j.jinf.2024.01.009. Epub 2024 Jan 30.

Disparities in COVID-19 mortality amongst the immunosuppressed: A systematic review and meta-analysis for enhanced disease surveillance

Meredith Leston  1 , Willam Elson  2 , Jose M Ordóñez-Mena  2 , Debasish Kar  2 , Heather Whitaker  3 , Mark Joy  2 , Nia Roberts  4 , F D Richard Hobbs  2 , Simon de Lusignan  2
Affiliations
Meta-Analysis

Disparities in COVID-19 mortality amongst the immunosuppressed: A systematic review and meta-analysis for enhanced disease surveillance

Meredith Leston et al. J Infect. 2024 Mar.

Abstract

Background: Effective disease surveillance, including that for COVID-19, is compromised without a standardised method for categorising the immunosuppressed as a clinical risk group.

Methods: We conducted a systematic review and meta-analysis to evaluate whether excess COVID-associated mortality compared to the immunocompetent could meaningfully subdivide the immunosuppressed. Our study adhered to UK Immunisation against infectious disease (Green Book) criteria for defining and categorising immunosuppression. Using OVID (EMBASE, MEDLINE, Transplant Library, and Global Health), PubMed, and Google Scholar, we examined relevant literature between the entirety of 2020 and 2022. We selected for cohort studies that provided mortality data for immunosuppressed subgroups and immunocompetent comparators. Meta-analyses, grey literature and any original works that failed to provide comparator data or reported all-cause or paediatric outcomes were excluded. Odds Ratios (OR) and 95% confidence intervals (CI) of COVID-19 mortality were meta-analysed by immunosuppressed category and subcategory. Subgroup analyses differentiated estimates by effect measure, country income, study setting, level of adjustment, use of matching and publication year. Study screening, extraction and bias assessment were performed blinded and independently by two researchers; conflicts were resolved with the oversight of a third researcher. PROSPERO registration number is CRD42022360755.

Findings: We identified 99 unique studies, incorporating data from 1,542,097 and 56,248,181 unique immunosuppressed and immunocompetent patients with COVID-19 infection, respectively. Compared to immunocompetent people (pooled OR, 95%CI), solid organ transplants (2.12, 1.50-2.99) and malignancy (2.02, 1.69-2.42) patients had a very high risk of COVID-19 mortality. Patients with rheumatological conditions (1.28, 1.13-1.45) and HIV (1.20, 1.05-1.36) had just slightly higher risks than the immunocompetent baseline. Case type, setting income and mortality data matching and adjustment were significant modifiers of excess immunosuppressed mortality for some immunosuppressed subgroups.

Interpretation: Excess COVID-associated mortality among the immunosuppressed compared to the immunocompetent was seen to vary significantly across subgroups. This novel means of subdivision has prospective benefit for targeting patient triage, shielding and vaccination policies during periods of high disease transmission.

Keywords: COVID-19; Covid; Digital health; Disease surveillance; Immunocompromised; Immunosuppressed; Pandemic preparedness; Personalised medicine; Vaccination; Vaccines.

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Conflict of interest statement

Declaration of Competing Interest The authors of this manuscript are all either directly employed by or affiliated with the Royal College of General Practitioners’ Research and Surveillance Centre (Oxford-RCGP RSC), the UK primary care sentinel network. This work originated as a direct response to the limitations of existing disease surveillance, both within the RSC and comparable networks, to monitor outcomes within the immunosuppressed with high resolution and fidelity. The findings of this work will now be validated within RSC data flows and amongst RSC collaborator groups. However, none of these stated actors or collaborators had any influence on the approach, analysis, interpretation or write-up of this work.

Figures

Fig. 1
Fig. 1
Study selection flow diagram.
Fig. 2
Fig. 2
Excess COVID-19 associated mortality by immunosuppressed category. *The column labelled as Cases indicates the total number of participants, immunosuppressed and immunocompetent combined. The column labelled as Mortalities indicates the total number of deaths registered in participants, immunosuppressed and immunocompetent combined. Instances of multiple-counts were not removed.
Fig. 3
Fig. 3
Excess COVID-19 associated mortality by immunosuppressed subcategory. *The column labelled as Cases indicates the total number of participants, immunosuppressed and immunocompetent combined. The column labelled as Mortalities indicates the total number of deaths registered in participants, immunosuppressed and immunocompetent combined. Instances of multiple-counts were not removed.
Fig. 4
Fig. 4
Excess COVID-19 associated mortality by immunosuppressed category and subcategory presented in descending order of effect size. *The column labelled as Cases indicates the total number of participants, immunosuppressed and immunocompetent combined. The column labelled as Mortalities indicates the total number of deaths registered in participants, immunosuppressed and immunocompetent combined. Instances of multiple-counts were not removed.
See this image and copyright information in PMC

Comment in

  • COVID-19 mortality amongst the immunosuppresed.
    Moreno-Torres V, Martínez-Urbistondo M, Calderón-Parra J, de Mendoza C, Soriano V. Moreno-Torres V, et al. J Infect. 2024 Apr;88(4):106137. doi: 10.1016/j.jinf.2024.106137. Epub 2024 Mar 11. J Infect. 2024. PMID: 38479495 No abstract available.

References

    1. Porter A., Akbari A., Carson‐Stevens A., Dale J., Dixon L., Edwards A., et al. Rationale for the shielding policy for clinically vulnerable people in the UK during the COVID-19 pandemic: a qualitative study. BMJ Open. 2023;13(8):e073464. doi: 10.1136/bmjopen-2023-073464. - DOI - PMC - PubMed
    1. Agrawal U., Bedston S., McCowan C., Oke J., Patterson L., Robertson C., et al. Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales. Lancet. 2022;400(10360):1305–1320. doi: 10.1016/S0140-6736(22)01656-7. - DOI - PMC - PubMed
    1. Truong T.T., Ryutov A., Pandey U., Yee R., Goldberg L., Bhojwani D., et al. Increased viral variants in children and young adults with impaired humoral immunity and persistent SARS-CoV-2 infection: A consecutive case series. EBioMedicine. 2021;67 doi: 10.1016/j.ebiom.2021.103355. - DOI - PMC - PubMed
    1. Furstenau L.B., Rabaioli B., Sott M.K., Cossul D., Bender M.S., Farina E.M.J.D.M., et al. A bibliometric network analysis of coronavirus during the first eight months of COVID-19 in 2020. Int J Environ Res Public Health. 2021;18(3):952. doi: 10.3390/ijerph18030952. - DOI - PMC - PubMed
    1. OECD. COVID-19: Protecting people and societies. OECD; 2020. Available at: https://www.oecd.org/coronavirus/policy-responses/covid-19-protecting-pe... [accessed November 12, 2023].

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