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      COVID-19 mortality in patients with immunodeficiency and its predictors: a systematic review

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          Abstract

          Introduction

          Patients with immunodeficiency are usually more prone to worse outcomes of infectious diseases. However, there are some disagreements in the context of COVID-19, for example, in patients with human immunodeficiency virus (HIV). Herein, we aimed to systematically review the risk and predictors of COVID-19 mortality in people with primary or secondary immunodeficiency.

          Methods

          PubMed, Scopus, Web of Science, and Science Direct were searched. We followed a two-step screening process to identify eligible results. We first reviewed the title and abstract of the records and the unqualified studies were removed. Then, their full texts were evaluated based on their coherence with the purpose and inclusion/exclusion criteria, and those eligible for qualitative synthesis were included.

          Results

          Twenty-two articles were included, which investigated a total of 109,326 with primary or secondary immunodeficiencies. Three studies investigated the pediatric and infant population, while other studies were conducted on the adult population. Overall, studies on both primary and secondary immunodeficiency conflicted as some reported higher and some mentioned lower mortality rates in patients with immunodeficiency.

          Conclusions

          Overall, there were two points of view in both types of immunodeficiencies. The first is the classical viewpoint that all immunodeficient patients are at a higher risk of infection leading to a higher mortality rate. The second types of studies found that immunodeficiency might play a less important or even an inverse role in mortality rates by lowering the severity of the inflammatory response. However, it is important to take note to comorbidities, such as DM, HTN, CAD, ESRD, history of lower respiratory infection, etc., and demographic factors, such as obesity and age > 70 years, as they appear to influence the mortality rate, especially in patients with secondary immunodeficiency.

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          Most cited references42

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          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

          Summary 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.
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            Coronavirus disease 2019 in patients with inborn errors of immunity: An international study

            Background There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense. Objective We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2. Methods An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI. Results We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died. Conclusions This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.
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              Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy

              This study describes the incidence and severity of COVID-19 among 77 590 HIV-positive patients receiving antiretroviral therapy (ART). These findings warrant further investigation of HIV ART in HIV preexposure prophylaxis studies and randomized trials among persons without HIV.
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                Author and article information

                Contributors
                s_a_alinaghi@yahoo.com
                karimi.amirali.1999@gmail.com
                barzegaryalireza@gmail.com
                Hengameh.mojdeganlou@gmail.com
                Farzinvahedi9@gmail.com
                mirghaderi76@gmail.com
                Parnian.shobeiri@gmail.com
                Mari_ramezani@yahoo.com
                Pyousefi97@yahoo.com
                pegah.mirzapour@yahoo.com
                macasty1234@gmail.com
                es.mehraeen@gmail.com
                omiddadras@yahoo.com
                voltarellifa@gmail.com
                Journal
                Eur J Med Res
                Eur J Med Res
                European Journal of Medical Research
                BioMed Central (London )
                0949-2321
                2047-783X
                8 October 2022
                8 October 2022
                2022
                : 27
                : 195
                Affiliations
                [1 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, , Tehran University of Medical Sciences, ; Tehran, Iran
                [2 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, School of Medicine, , Tehran University of Medical Sciences, ; Tehran, Iran
                [3 ]GRID grid.411463.5, ISNI 0000 0001 0706 2472, School of Medicine, , Islamic Azad University, ; Tehran, Iran
                [4 ]GRID grid.412763.5, ISNI 0000 0004 0442 8645, Department of Pathology, , Urmia University of Medical Sciences, ; Urmia, Iran
                [5 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Health Management, Policy & Economics,, School of Public Health, , Tehran University of Medical Sciences, ; Tehran, Iran
                [6 ]GRID grid.444768.d, ISNI 0000 0004 0612 1049, Department of Health Information Management, Faculty of Paramedical, , Kashan University of Medical Sciences, ; Kashan, Iran
                [7 ]GRID grid.8652.9, ISNI 0000 0004 1937 1485, Biomedical Engineering Unit, , University of Ghana Medical Center (UGMC), ; Accra, Ghana
                [8 ]Department of Health Information Technology, Khalkhal University of Medical Sciences, Khalkhal, Iran
                [9 ]GRID grid.7914.b, ISNI 0000 0004 1936 7443, Department of Global Public Health and Primary Care, , University of Bergen, ; Bergen, Norway
                [10 ]GRID grid.411206.0, ISNI 0000 0001 2322 4953, Graduation Program in Health Sciences, Faculty of Medicine, , Federal University of Mato Grosso, ; Cuiabá, Mato Grosso Brazil
                Author information
                http://orcid.org/0000-0003-4108-2973
                Article
                824
                10.1186/s40001-022-00824-7
                9547631
                36209202
                1c7f1a9f-11cc-4504-a54b-f0e4a4c16de4
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 6 August 2021
                : 24 September 2022
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Medicine
                covid-19,immunocompromised,immunodeficiency,immunosuppression,impaired immune response,sars-cov-2,comorbidities

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