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      The role of trained immunity in COVID-19: Lessons for the next pandemic

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          Abstract

          Trained immunity is a long-term increase in responsiveness of innate immune cells, induced by certain infections and vaccines. During the last 3 years of the COVID-19 pandemic, vaccines that induce trained immunity, such as BCG, MMR, OPV, and others, have been investigated for their capacity to protect against COVID-19. Further, trained immunity-inducing vaccines have been shown to improve B and T cell responsiveness to both mRNA- and adenovirus-based anti-COVID-19 vaccines. Moreover, SARS-CoV-2 infection itself induces inappropriately strong programs of trained immunity in some individuals, which may contribute to the long-term inflammatory sequelae. In this review, we detail these and other aspects of the role of trained immunity in SARS-CoV-2 infection and COVID-19. We also examine the learnings from the trained immunity studies conducted in the context of this pandemic and discuss how they may help us in preparing for future infectious outbreaks.

          Abstract

          Trained immunity-inducing vaccines have been suggested to protect against heterologous infections, including COVID-19. This review presents the studies performed during the pandemic that have investigated the effects of vaccines such as BCG, OPV, MMR, and others against COVID-19. In addition, data are reviewed that suggest that COVID-19 itself and the novel COVID-19 vaccines can also induce trained immunity programs.

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          Most cited references100

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          Clinical and immunologic features in severe and moderate Coronavirus Disease 2019

          Journal of Clinical Investigation
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            Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure

            Summary Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation.
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              Defining trained immunity and its role in health and disease

              Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed ‘trained immunity’, a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define ‘trained immunity’ as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
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                Author and article information

                Journal
                Cell Host Microbe
                Cell Host Microbe
                Cell Host & Microbe
                Elsevier Inc.
                1931-3128
                1934-6069
                14 June 2023
                14 June 2023
                14 June 2023
                : 31
                : 6
                : 890-901
                Affiliations
                [1 ]Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
                [2 ]Department of Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, Bonn, Germany
                [3 ]Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark, Copenhagen, Denmark
                [4 ]Danish Institute for Advanced Study, University of Southern Denmark, Odense, Denmark
                [5 ]4 th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
                [6 ]Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
                [7 ]Departments of Pediatrics and Biomedical Sciences, Guerin Children’s and Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, USA
                [8 ]Office of Vaccines Research and Review, Food and Drug Administration, Global Virus Network Center of Excellence, Silver Spring, MD, USA
                [9 ]Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
                [10 ]Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Global Virus Network, Baltimore, MD, USA
                Author notes
                []Corresponding author
                Article
                S1931-3128(23)00197-X
                10.1016/j.chom.2023.05.004
                10265767
                37321172
                d552f3e7-d0aa-4732-aba4-220a0f12aee9
                © 2023 Elsevier Inc.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Categories
                Review

                Microbiology & Virology
                trained immunity,covid-19,vaccines,bcg,clinical trials
                Microbiology & Virology
                trained immunity, covid-19, vaccines, bcg, clinical trials

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