Limited induction of SARS-CoV-2–specific T cell responses in children with multisystem inflammatory syndrome compared with COVID-19

Singh, Vidisha; Obregon-Perko, Veronica; Lapp, Stacey A.; Horner, Anna; Brooks, Angelique L.; Macoy, Lisa; Hussaini, Laila; Lu, Austin; Gibson, Theda; Silvestri, Guido; Grifoni, Alba; Weiskopf, Daniela; Sette, Alessandro; Anderson, Evan J.; Rostad, Christina A.; Chahroudi, Ann

doi:10.1172/jci.insight.155145

Cited by 20 publications

(24 citation statements)

References 41 publications

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“…T cell receptor repertoire analyses have led to the hypothesis that the SARS-CoV-2 spike protein has a superantigen effect, causing T cell dysregulation that contributes to the development of MIS-C 15 . Finally, flow cytometry analyses have demonstrated that children with MIS-C have reduced virus-specific CD4+ and CD8+ T cells compared to children with COVID-19 and controls 16 .…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Nucleic acid biomarkers of immune response and cell and tissue damage in COVID-19 and MIS-C

Loy

Sotomayor-González

Servellita

et al. 2022

Preprint

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Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with acute COVID-19 (n=70) or MIS-C (n=141) across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between these two disease states, with increased heterogeneity and multi-organ involvement in MIS-C encompassing diverse cell types such as endothelial and neuronal Schwann cells. Whole blood RNA profiling reveals upregulation of similar pro-inflammatory signaling pathways in COVID-19 and MIS-C, but also MIS-C specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole blood RNA in paired samples yields different yet complementary signatures for each disease state. Our work provides a systems-level, multi-analyte view of immune responses and tissue damage in COVID-19 and MIS-C and informs the future development of new disease biomarkers.

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Nucleic acid biomarkers of immune response and cell and tissue damage in COVID-19 and MIS-C

Loy

Sotomayor-González

Servellita

et al. 2022

Preprint

Self Cite

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“…In brief, PBMCs were seeded in duplicate in 96-well plates (2x10 5 cells/well) and stimulated for 48 h with pools of SARS-CoV-2 S protein peptides or N protein peptides (2 μg/ml per peptide, see Supplementary Table S2 ). The T cell peptides used in this study were identified by sequence homology and by a priori epitope prediction using bioinformatics approaches to identify potential targets for immune responses to the SARS-CoV-2 ( 23 ), and it has been widely recognized ( 24 – 26 ). An anti-CD3 monoclonal antibody (mAb) was used as a positive control, and RPMI 1640 medium was used as a negative control.…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Dynamics of Cellular Responses in Recovered COVID-19 Patients

et al. 2022

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Safe and effective vaccines and therapeutics based on the understanding of antiviral immunity are urgently needed to end the COVID-19 pandemic. However, the understanding of these immune responses, especially cellular immune responses to SARS-CoV-2 infection, is limited. Here, we conducted a cohort study of COVID-19 patients who were followed and had blood collected to characterize the longitudinal dynamics of their cellular immune responses. Compared with healthy controls, the percentage of activation of SARS-CoV-2 S/N-specific T cells in recovered patients was significantly higher. And the activation percentage of S/N-specific CD8+ T cells in recovered patients was significantly higher than that of CD4+ T cells. Notably, SARS-CoV-2 specific T-cell responses were strongly biased toward the expression of Th1 cytokines, included the cytokines IFNγ, TNFα and IL2. Moreover, the secreted IFNγ and IL2 level in severe patients was higher than that in mild patients. Additionally, the number of IFNγ-secreting S-specific T cells in recovered patients were higher than that of N-specific T cells. Overall, the SARS-CoV-2 S/N-specific T-cell responses in recovered patients were strong, and virus-specific immunity was present until 14-16 weeks after symptom onset. Our work provides a basis for understanding the immune responses and pathogenesis of COVID-19. It also has implications for vaccine development and optimization and speeding up the licensing of the next generation of COVID-19 vaccines.

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“…There is conflicting evidence regarding the functional capacity of the antibody responses in children, while some studies reported neutralizing antibody responses of lower magnitude in children, 43,44 other studies observed comparable plasma antibody responses and neutralizing antibody titers in children and adults. 45,46 Several studies have documented that SARS-CoV-2-specific T cell responses are reduced in children compared with adults. 46,47 Both the frequencies of CD4 + and CD8 + T cell responses to SARS-CoV-2 structural and ORF1ab proteins are lower in infants compared with adults when IFNγ production or T cell activation are assessed, and infants also have lower frequencies of effector memory CD4 + T cells.…”

Section: Robus T Immunit Y To Sar S -Cov-2 Infec Ti On and Vaccinati ...mentioning

confidence: 99%

“…47 T cell responses persist and increase with time post infection in both age groups. 47 The impact on disease severity on T cell responses requires further clarification as both reduced 46 and stronger 48 Pediatric immunity to SARS-CoV-2 mRNA-LNP vaccination has also proven to be robust, as demonstrated in the Pfizer and Moderna mRNA-LNP dosing studies in children ages 5-11 where vaccine doses of half or less than that used in adults were able to achieve similar spike-specific IgG responses and neutralizing titers. 49,50 Moreover, pre-fusion stabilized Spike mRNA-LNP vaccination of 2 month-old nonhuman primates at a lower dose than studied in pre-clinical adult nonhuman primate vaccines achieved high magnitude and durable binding and neutralizing antibody responses.…”

Section: Robus T Immunit Y To Sar S -Cov-2 Infec Ti On and Vaccinati ...mentioning

confidence: 99%

“…These findings have implications for serology testing approaches to confirm prior SARS‐CoV‐2 infection. There is conflicting evidence regarding the functional capacity of the antibody responses in children, while some studies reported neutralizing antibody responses of lower magnitude in children, 43,44 other studies observed comparable plasma antibody responses and neutralizing antibody titers in children and adults 45,46 …”

Section: Robust Immunity To Sars‐cov‐2 Infection and Vaccination In C...mentioning

confidence: 99%

See 1 more Smart Citation

Routine SARS‐CoV‐2 vaccination for all children*

Paris

Permar

2022

Immunological Reviews

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The SARS-CoV-2 pandemic has resulted in unprecedented health and economic losses. Children generally present with less severe disease from this virus compared with adults, yet neonates and children with COVID-19 can require hospitalization, and older children can develop severe complications, such as the multisystem inflammatory syndrome, resulting in >1500 deaths in children from COVID-19 since the onset of the pandemic. The introduction of effective SARS-CoV-2 vaccines in school-age children and adult populations combined with the emergence of new, more highly transmissible SARS-CoV-2 variants has resulted in a proportional increase of infections in young children. Here, we discuss (1) the current knowledge on pediatric SARS-CoV-2 infection and pathogenesis in comparison with adults, (2) the data on vaccine immunogenicity and efficacy in children, and (3) the benefits of early life SARS-CoV-2 vaccination. K E Y W O R D S children, infant immunity, MIS-C, SARS-CoV-2, vaccines *This article is part of a series of reviews covering SARS-CoV-2 Immunity appearing in Volume 309 of Immunological Reviews.

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Limited induction of SARS-CoV-2–specific T cell responses in children with multisystem inflammatory syndrome compared with COVID-19

Cited by 20 publications

References 41 publications

WITHDRAWN: Nucleic acid biomarkers of immune response and cell and tissue damage in COVID-19 and MIS-C

WITHDRAWN: Nucleic acid biomarkers of immune response and cell and tissue damage in COVID-19 and MIS-C

Longitudinal Dynamics of Cellular Responses in Recovered COVID-19 Patients

Routine SARS‐CoV‐2 vaccination for all children*

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