The role of the thymus in COVID-19 disease severity: implications for antibody treatment and immunization

Kellogg, Caitlyn; Equils, Ozlem

doi:10.1080/21645515.2020.1818519

Cited by 39 publications

(36 citation statements)

References 77 publications

(109 reference statements)

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“…The effect of aging on the thymus and immune senescence is well established, and the resulting inflammaging is found to be implicated in the development of many chronic diseases (Gunes et al, 2020;Kellogg and Equils, 2020). Both aging and diseases of inflammaging are associated with severe COVID-19, and a dysfunctional thymus may be implicated in the unfavorable outcome of disease (Gunes et al, 2020;Kellogg and Equils, 2020). Of note, MX1 plays an important role in the thymus as part of the innate antiviral immune response.…”

Section: Discussionmentioning

confidence: 99%

Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19

et al. 2021

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The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex and comorbidities, but they do not fully explain the wide spectrum of disease manifestations. Genetic factors implicated in the host antiviral response provide for novel insights into its pathogenesis. We performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data, including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 and near MX1 gene show associations with severe COVID-19. The minor alleles of the five SNPs correlated with a reduced risk of developing severe COVID-19 and high level of MX1 expression in blood. Our findings demonstrate that host genetic factors can influence the different clinical presentations of COVID-19 and that MX1 could be a potential therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19

et al. 2021

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“…The effect of aging on the thymus and immune senescence is well established, and the resulting inflammaging is found to be implicated in the development of many chronic diseases. Both aging and diseases of inflammaging are associated with severe COVID-19, and a dysfunctional thymus may be implicated in the unfavorable outcome of disease (19, 20). Thus, our finding suggests that the identified SNPs could be severe COVID-19 risk factors also for their implications in the thymus function.…”

Section: Discussionmentioning

confidence: 99%

Common variants at 21q22.3 locus influenceMX1gene expression and susceptibility to severe COVID-19

Andolfo

Russo

Lasorsa

et al. 2020

Preprint

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The COVID-19 disease, caused by the SARS-Cov-2, presents a heterogeneous clinical spectrum. The risk factors do not fully explain the wide spectrum of disease manifestations, so it is possible that genetic factors could account for novel insights into its pathogenesis.In our previous study, we hypothesized that common variants on chromosome 21, near TMPRSS2 and MX1 genes, may be genetic risk factors associated to the different clinical manifestations of COVID-19. Here, we performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms (SNPs) within TMPRSS2 and near MX1 gene show suggestive associations (P≤1×10−5) with severe COVID-19. All five SNPs replicated the association in two independent cohorts of Asian subjects while two and one out of the 5 SNPs replicated in African and Italian populations, respectively (P≤0.05). The minor alleles of these five SNPs correlated with a reduced risk of developing severe COVID-19 and increased level of MX1 expression in blood.Our findings provide further evidence that host genetic factors can contribute to determine the different clinical presentations of COVID-19 and that MX1, an antiviral effector of type I and III interferon pathway, may be a potential therapeutic target.

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“…Indeed, our investigations have shown that in mice with thymic involution, there was increased lymphocyte infiltration into self-tissues, including the lung [ 67 ]. Although there is increasing interest in the correlation between immunosenescence and the increased risk of COVID-19 mortality in the elderly, more research is needed to fully elucidate the role of pre-existing lung inflammation and infiltration of potentially self-reactive T cells during COVID-19 pathogenesis [ 73 , 74 , 75 , 76 ].…”

Section: How Does Age-related Thymic Involution and Subsequent T-cmentioning

confidence: 99%

“…Currently there are several proposed immune interventions for rebooting anti-COVID-19 immunity mostly focused on enhancing T effector cell responses and ameliorating immune cell-induced cytokine storm [ 15 , 87 ], which is more deadly in the elderly. Given that there appears to be profound T cell dysfunction in severe, particularly in aged, COVID-19 cases [ 32 , 88 , 89 ], rebooting T cell function by restoring thymic function should be considered as a potential holistic treatment for improving antiviral immunity and vaccination efficiency and potentially improve COVID-19 prognosis [ 76 ]. Along with rejuvenation of aged thymic function, refreshing the peripheral senescent T cell system, enhancing immune homeostasis, and reducing chronic peripheral inflammation, is also important for boosting antiviral immunity and vaccination efficiency [ 3 , 17 , 18 ].…”

Section: How Can We Sufficiently Restore Antiviral Immunity and Immentioning

confidence: 99%

Thymic Aging May Be Associated with COVID-19 Pathophysiology in the Elderly

Wang

Thomas

et al. 2021

Cells

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global pandemic of coronavirus disease 2019 (COVID-19) and particularly exhibits severe symptoms and mortality in elderly individuals. Mounting evidence shows that the characteristics of the age-related clinical severity of COVID-19 are attributed to insufficient antiviral immune function and excessive self-damaging immune reaction, involving T cell immunity and associated with pre-existing basal inflammation in the elderly. Age-related changes to T cell immunosenescence is characterized by not only restricted T cell receptor (TCR) repertoire diversity, accumulation of exhausted and/or senescent memory T cells, but also by increased self-reactive T cell- and innate immune cell-induced chronic inflammation, and accumulated and functionally enhanced polyclonal regulatory T (Treg) cells. Many of these changes can be traced back to age-related thymic involution/degeneration. How these changes contribute to differences in COVID-19 disease severity between young and aged patients is an urgent area of investigation. Therefore, we attempt to connect various clues in this field by reviewing and discussing recent research on the role of the thymus and T cells in COVID-19 immunity during aging (a synergistic effect of diminished responses to pathogens and enhanced responses to self) impacting age-related clinical severity of COVID-19. We also address potential combinational strategies to rejuvenate multiple aging-impacted immune system checkpoints by revival of aged thymic function, boosting peripheral T cell responses, and alleviating chronic, basal inflammation to improve the efficiency of anti-SARS-CoV-2 immunity and vaccination in the elderly.

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The role of the thymus in COVID-19 disease severity: implications for antibody treatment and immunization

Cited by 39 publications

References 77 publications

Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19

Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19

Common variants at 21q22.3 locus influenceMX1gene expression and susceptibility to severe COVID-19

Thymic Aging May Be Associated with COVID-19 Pathophysiology in the Elderly

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