Ventura Lucas Haniel A, Torres Lícia, Camatta Giovanna Caliman, Zamame Jofer, Coelho Monique Macedo, Ramalho-Pinto Cecília Horta, Gervazio João, Caixeta Felipe, Nascimento Leandro, Oliveira Mariana Almeida, Martins Vinícius Dantas, Oliveira Marcos Felipe, Costa Murilo Soares, Sato Hugo Itaru, Guimarães Henrique Cerqueira, Barbuto Rafael Calvão, Veiga Ana Paula Rocha, Ataíde Najara, Caetano Gabriela Prandi, Rangon Sarah, Júnior Mauro Lúcio O, Fortes Fernanda Calvo, Zuccherato Luciana, Speziali Elaine, Martins-Filho Olindo Assis, Coelho Verônica, Avritchir Roberto, Souza Rafael, Ayupe Marina, Loureiro Caio, Passos Maria Eduarda, Neves Ana Clara Mota, Leite Pauline, Teixeira Santuza Maria Ribeiro, Tupinambás Unaí, Felicori Liza Figueiredo, Silveira-Nunes Gabriela, Maioli Tatiani Uceli, Fonseca Denise Morais, Teixeira-Carvalho Andrea, Faria Ana Maria Caetano
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
Aging Cell. 2025 Jul;24(7):e70077. doi: 10.1111/acel.70077. Epub 2025 May 19.
In this study, we tested the hypothesis that the immunosenescence profile could account for the disproportional susceptibility of the elderly to severe forms of COVID-19. The immunological profiles of volunteers residing in endemic and non-endemic areas for chronic infectious diseases were analyzed at the early stage of SARS-CoV-2 infection. A unique signature of inflammatory plasma mediators was identified in COVID-19 volunteers when compared to individuals with other flu-like syndromes. COVID-19 severity correlated with high levels of inflammatory mediators; among them, CXCL9, a serum marker of aging. Patients who progressed to hospitalization displayed high frequencies of CD8 and CD4 T cells expressing exhaustion and senescence markers and showed reduced and more mature B cell repertoires, which are typical of senescence. They also had an acceleration of epigenetic age measured by DNA methylation. Therefore, severe COVID-19 correlated with phenotypic, functional, and epigenetic features of accelerated immunosenescence at the onset of infection.
在本研究中，我们检验了以下假设：免疫衰老特征可解释老年人对重症COVID-19的易感性不成比例的现象。在SARS-CoV-2感染的早期阶段，分析了居住在慢性传染病流行地区和非流行地区的志愿者的免疫特征。与患有其他流感样综合征的个体相比，在COVID-19志愿者中发现了炎症性血浆介质的独特特征。COVID-19的严重程度与高水平的炎症介质相关；其中，CXCL9是一种衰老的血清标志物。进展为住院治疗的患者中，表达耗竭和衰老标志物的CD8和CD4 T细胞频率较高，且B细胞库减少且更加成熟，这是衰老的典型特征。他们的DNA甲基化测量的表观遗传年龄也加速了。因此，重症COVID-19与感染开始时加速免疫衰老的表型、功能和表观遗传特征相关。
