9
views
0
recommends
+1 Recommend
2 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          SARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults are unclear. Here, we report SARS-CoV-2 specific T cell responses in infected adults and children and find that the acute and memory CD4 + T cell responses to structural SARS-CoV-2 proteins increase with age, whereas CD8 + T cell responses increase with time post-infection. Infected children have lower CD4 + and CD8 + T cell responses to SARS-CoV-2 structural and ORF1ab proteins when compared with infected adults, comparable T cell polyfunctionality and reduced CD4 + T cell effector memory. Compared with adults, children have lower levels of antibodies to β-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses are increased, whilst monocyte numbers are reduced, indicating rapid adaptive co-ordination of the T and B cell responses and differing levels of inflammation. Therefore, reduced prior β-coronavirus immunity and reduced T cell activation in children might drive milder COVID-19 pathogenesis.

          Abstract

          Why children are generally less susceptible than adults to COVID-19 is unclear and has not extensively been examined longitudinally. Here the authors compare antibodies, cytokines and immune cell responses in adults and children over 6 months post-infection showing, among other things, a reduced CD4+ and CD8+ T cell response in children.

          Related collections

          Most cited references50

          • Record: found
          • Abstract: found
          • Article: not found

          Clinical and immunologic features in severe and moderate Coronavirus Disease 2019

          Journal of Clinical Investigation
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

            Summary Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals

              Summary Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide ‘megapools’, circulating SARS-CoV-2−specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2−reactive CD4+ T cells in ∼40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS-CoV-2.
                Bookmark

                Author and article information

                Contributors
                sophiev@hku.hk
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                29 July 2021
                29 July 2021
                2021
                : 12
                : 4678
                Affiliations
                [1 ]GRID grid.194645.b, ISNI 0000000121742757, HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, , The University of Hong Kong, ; Hong Kong, SAR China
                [2 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Department of Medicine and Therapeutics, Prince of Wales Hospital, , Chinese University of Hong Kong, ; Hong Kong, SAR China
                [3 ]GRID grid.415229.9, ISNI 0000 0004 1799 7070, Department of Paediatric and Adolescent Medicine, , Hong Kong Hospital Authority Infectious Disease Center, Princess Margaret Hospital, ; Hong Kong, SAR, China
                [4 ]GRID grid.415229.9, ISNI 0000 0004 1799 7070, Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, ; Hong Kong SAR, China
                [5 ]GRID grid.414370.5, ISNI 0000 0004 1764 4320, Department of Paediatric and Adolescent Medicine, , The University of Hong Kong and Queen Mary Hospital, Hospital Authority of Hong Kong, ; Hong Kong SAR, China
                [6 ]GRID grid.414370.5, ISNI 0000 0004 1764 4320, Department of Paediatrics, Queen Elizabeth Hospital, , Hospital Authority of Hong Kong, ; Hong Kong SAR, China
                [7 ]GRID grid.194645.b, ISNI 0000000121742757, WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, , The University of Hong Kong, ; Hong Kong, SAR China
                [8 ]GRID grid.194645.b, ISNI 0000000121742757, Division of Public Health Laboratory Sciences, School of Public Health, Li Ka Shing Faculty of Medicine, , The University of Hong Kong, ; Hong Kong, SAR China
                Author information
                https://orcid.org/http://orcid.org/0000-0003-4382-2445
                https://orcid.org/http://orcid.org/0000-0002-1476-9625
                https://orcid.org/http://orcid.org/0000-0002-9256-4799
                https://orcid.org/http://orcid.org/0000-0002-5471-9139
                https://orcid.org/http://orcid.org/0000-0002-6688-9637
                https://orcid.org/http://orcid.org/0000-0002-9101-7953
                https://orcid.org/http://orcid.org/0000-0001-8217-5995
                https://orcid.org/http://orcid.org/0000-0002-0768-9926
                Article
                24938
                10.1038/s41467-021-24938-4
                8322064
                34326343
                4ec71719-1416-43a1-8f99-0435b372dc9a
                © The Author(s) 2021

                Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 February 2021
                : 14 July 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100005847, Food and Health Bureau of the Government of the Hong Kong Special Administrative Region | Health and Medical Research Fund (HMRF);
                Award ID: COVID-190115
                Award ID: COVID-190126
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                cellular immunity,viral infection
                Uncategorized
                cellular immunity, viral infection

                Comments

                Comment on this article