RESUMO
The functional relevance of preexisting cross-immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a subject of intense debate. Here, we show that human endemic coronavirus (HCoV)reactive and SARS-CoV-2cross-reactive CD4+ T cells are ubiquitous but decrease with age. We identified a universal immunodominant coronavirus-specific spike peptide (S816-830) and demonstrate that preexisting spike- and S816-830reactive T cells were recruited into immune responses to SARS-CoV-2 infection and their frequency correlated with antiSARS-CoV-2-S1-IgG antibodies. Spikecross-reactive T cells were also activated after primary BNT162b2 COVID-19 messenger RNA vaccination and displayed kinetics similar to those of secondary immune responses. Our results highlight the functional contribution of preexisting spikecross-reactive T cells in SARS-CoV-2 infection and vaccination. Cross-reactive immunity may account for the unexpectedly rapid induction of immunity after primary SARS-CoV-2 immunization and the high rate of asymptomatic or mild COVID-19 disease courses.
Assuntos
Linfócitos T CD4-Positivos/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Vacina BNT162 , Complexo CD3/imunologia , Vacinas contra COVID-19/imunologia , Reações Cruzadas , Feminino , Humanos , Imunidade , Epitopos Imunodominantes/imunologia , Masculino , Pessoa de Meia-Idade , Fases de Leitura Aberta , Fragmentos de Peptídeos/imunologia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação , Adulto JovemRESUMO
If age boundaries are arbitrarily or roughly defined, age-related analyses can result in questionable findings. Here, we aimed to delineate the uniquely age-dependent immune features of coronavirus disease 2019 (COVID-19) in a retrospective study of 447 patients, stratified according to age distributions of COVID-19 morbidity statistics into well-defined age-cohorts (2-25y, 26-38y, 39-57y, 58-68y, and 69-79y). Age-dependent susceptibilities and severities of the disease were observed in COVID-19 patients. A comparison of the lymphocyte counts among the five age-groups indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection led to age-dependent lymphopenia. Among the lymphocyte subsets, the CD8+ T cell count alone was significantly and age-dependently decreased (520, 385, 320, 172, and 139 n/µl in the five age-groups, respectively). In contrast, the CD4+ T cell, B cell, and natural killer cell counts did not differ among age-cohorts. Age and CD8+ T cell counts (r=â0.435, p<0.0001) were negatively correlated in COVID-19 patients. Moreover, SARS-CoV-2 infection age-dependently increased the plasma C-reactive protein concentrations (2.0, 5.0, 9.0, 11.6, and 36.1 mg/L in the five age-groups, respectively). These findings can be used to elucidate the role of CD8+ T cells in age-related pathogenesis and to help develop therapeutic strategies for COVID-19.
Assuntos
Distribuição por Idade , Complexo CD3/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/complicações , Linfopenia/complicações , Admissão do Paciente , Adolescente , Adulto , Idoso , COVID-19/virologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Contagem de Linfócitos , Linfopenia/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Adulto JovemAssuntos
COVID-19/imunologia , Células Matadoras Naturais/imunologia , Subpopulações de Linfócitos/imunologia , Antígenos CD19/imunologia , Povo Asiático , Linfócitos B/imunologia , Contagem de Células Sanguíneas , Complexo CD3/imunologia , Linfócitos T CD4-Positivos/imunologia , Antígeno CD56/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/epidemiologia , COVID-19/fisiopatologia , Feminino , Citometria de Fluxo , Corantes Fluorescentes/química , Proteínas Ligadas por GPI/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Receptores de IgG/imunologiaRESUMO
BACKGROUND: We observe changes of the main lymphocyte subsets (CD16+CD56ãCD19ãCD3ãCD4ãand CD8) in COVID-19-infected patients and explore whether the changes are associated with disease severity. METHODS: One-hundred and fifty-four cases of COVID-19-infected patients were selected and divided into 3 groups (moderate group, severe group and critical group). The flow cytometry assay was performed to examine the numbers of lymphocyte subsets. RESULTS: CD3+, CD4+ and CD8 + T lymphocyte subsets were decreased in COVID-19-infected patients. Compared with the moderate group and the sever group, CD3+, CD4+ and CD8+ T cells in the critical group decreased greatly (P < 0.001, P = 0.005 or P = 0.001). CONCLUSIONS: Reduced CD3+, CD4+, CD8+ T lymphocyte counts may reflect the severity of the COVID-19. Monitoring T cell changes has important implications for the diagnosis and treatment of severe patients who may become critically ill.