Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19

Khoo, Weng Hua; Jackson, Katherine; Phetsouphanh, Chansavath; Zaunders, John; Alquicira-Hernández, José; Yazar, Seyhan; Ruiz-Diaz, Stephanie; Singh, Mandeep; Dhenni, Rama; Kyaw, Wunna; Tea, Fiona; Merheb, Vera; Lee, Fiona X Z; Burrell, Rebecca A.; Howard‐Jones, Annaleise R.; Koirala, Archana; Zhou, Li; Yuksel, Aysen; Catchpoole, Daniel; Lai, Catherine L.; Vitagliano, Tennille L; Rouet, Romain; Christ, Daniel; Tang, Benjamin; West, Nicholas P.; George, Shane; Gerrard, John; Croucher, Peter I.; Kelleher, Anthony D.; Goodnow, Christopher G.; Sprent, Jonathan; Powell, Joseph E.; Brilot, Fabienne; Nanan, Ralph; Hsu, Peter; Deenick, Elissa K.; Britton, Philip N; Phan, Tri Giang

doi:10.1016/j.clim.2022.109209

Cited by 23 publications

(26 citation statements)

References 109 publications

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“…In combination with the relative lack of a robust T‐cell response in asymptomatic and mild disease patients here, this may question the necessity of a strong T‐cell response to prevent the progression of COVID‐19. This is consistent with the diverse polyclonal, less differentiated SARS‐CoV‐2 specific T‐cell response observed in children with mild and asymptomatic T‐cell response than the clonally expanded memory T‐cell response with markers of cytotoxicity and exhaustion present in adults 46 . The protective capacity of T cells should be investigated further to assess whether preserved T‐cell response against variant SARS‐CoV‐2 viruses provide protection against severe disease, as has been suggested previously 12,13,16 …”

Section: Discussionsupporting

confidence: 85%

A unique cytotoxic CD4⁺ T cell‐signature defines critical COVID‐19

Baird,

Ashley,

Marsh‐Wakefield

et al. 2023

Clin & Trans Imm

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ObjectivesSARS‐CoV‐2 infection causes a spectrum of clinical disease presentation, ranging from asymptomatic to fatal. While neutralising antibody (NAb) responses correlate with protection against symptomatic and severe infection, the contribution of the T‐cell response to disease resolution or progression is still unclear. As newly emerging variants of concern have the capacity to partially escape NAb responses, defining the contribution of individual T‐cell subsets to disease outcome is imperative to inform the development of next‐generation COVID‐19 vaccines.MethodsImmunophenotyping of T‐cell responses in unvaccinated individuals was performed, representing the full spectrum of COVID‐19 clinical presentation. Computational and manual analyses were used to identify T‐cell populations associated with distinct disease states.ResultsCritical SARS‐CoV‐2 infection was characterised by an increase in activated and cytotoxic CD4+ lymphocytes (CTL). These CD4+ CTLs were largely absent in asymptomatic to severe disease states. In contrast, non‐critical COVID‐19 was associated with high frequencies of naïve T cells and lack of activation marker expression.ConclusionHighly activated and cytotoxic CD4+ T‐cell responses may contribute to cell‐mediated host tissue damage and progression of COVID‐19. Induction of these potentially detrimental T‐cell responses should be considered when developing and implementing effective COVID‐19 control strategies.

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Section: Discussionsupporting

confidence: 85%

A unique cytotoxic CD4⁺ T cell‐signature defines critical COVID‐19

Baird,

Ashley,

Marsh‐Wakefield

et al. 2023

Clin & Trans Imm

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“…Differences in circulating lymphocyte populations and cytokine levels were observed in patients similarly treated with steroids as reported [33][34]. Increased levels of IL-10 and a decreased amount of CD4 were recorded.…”

Section: Discussionmentioning

confidence: 55%

SARS-CoV-2 Infection in Venezuelan Pediatric Patients: A Single Center Prospective Observational Study

Crespo¹,

Mayora²,

Sanctis³

et al. 2023

Preprint

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Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A correlation was found between IL-10 and IL-6 concentrations and age group; lymphocyte subpopulations and nutritional status and steroid use; IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.

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“…This is consistent with the diverse polyclonal, less differentiated SARS-CoV-2 specific T cell response observed in children with mild and asymptomatic T cell response than the clonally expanded memory T cell response with markers of cytotoxicity and exhaustion present in adults. 46 The protective capacity of T cells should be investigated further to assess whether preserved T cell response against variant SARS-CoV-2 viruses provide protection against severe disease, as has been suggested previously. 12,13,16 Finally, there are several clinical variables that may confound this analysis, notably the impact of age on the immune response to infection.…”

Section: Discussionmentioning

confidence: 95%

A unique cytotoxic CD4⁺T cells signature defines critical COVID-19

Baird

Ashley

Marsh‐Wakefield

et al. 2023

Preprint

View full text Add to dashboard Cite

Background and objectives. SARS-CoV-2 infection causes a spectrum of clinical disease presentation, ranging from asymptomatic to fatal. While neutralising antibody (NAb) responses correlate with protection against symptomatic and severe infection, the contribution of the T cell response to the resolution or progression of disease is still unclear. Optimal protective immunity may require activation of distinct immune pathways. As such, defining the contribution of individual T cell subsets to disease outcome is imperative to inform the development of next-generation COVID-19 vaccines. To address this, we performed immunophenotyping of T cell responses in unvaccinated individuals, representing the full spectrum of COVID-19 clinical presentation. Methods. Spectral cytometry was performed on peripheral blood mononuclear cell samples from patients with PCR-confirmed SARS-CoV-2 infection. Computational and manual analyses were used to identify T cell populations associated with distinct disease states through unbiased clustering, principal component analysis and discriminant analysis. Results. Critical SARS-CoV-2 infection was characterised by an increase in activated and cytotoxic CD4+ (CTL) cells of a T follicular helper (TFH) or effector memory re-expressing CD45RA (TEMRA) phenotype. These CD4+ CTLs were largely absent in those with less severe disease. In contrast, those with asymptomatic or mild disease were associated with high proportions of naive T cells and reduced expression of activation markers. Conclusion. Highly activated and cytotoxic CD4+ T cell responses may contribute to cell-mediated host tissue damage and progression of COVID-19. Potential for induction of these detrimental T cell responses should be considered when developing and implementing effective COVID-19 control strategies.

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Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19

Cited by 23 publications

References 109 publications

A unique cytotoxic CD4⁺ T cell‐signature defines critical COVID‐19

A unique cytotoxic CD4⁺ T cell‐signature defines critical COVID‐19

SARS-CoV-2 Infection in Venezuelan Pediatric Patients: A Single Center Prospective Observational Study

A unique cytotoxic CD4⁺T cells signature defines critical COVID-19

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Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19

Cited by 23 publications

References 109 publications

A unique cytotoxic CD4+ T cell‐signature defines critical COVID‐19

A unique cytotoxic CD4+ T cell‐signature defines critical COVID‐19

SARS-CoV-2 Infection in Venezuelan Pediatric Patients: A Single Center Prospective Observational Study

A unique cytotoxic CD4+T cells signature defines critical COVID-19

Contact Info

Product

Resources

About

A unique cytotoxic CD4⁺ T cell‐signature defines critical COVID‐19

A unique cytotoxic CD4⁺ T cell‐signature defines critical COVID‐19

A unique cytotoxic CD4⁺T cells signature defines critical COVID-19