Gasull Magda, Pumarega José, Aguilar Ruth, Campi Laura, Prieto-Merino David, Villar-García Judit, Rius Cristina, Bolúmar Francisco, Trasande Leonardo, Dobaño Carlota, Moncunill Gemma, Porta Miquel
Hospital del Mar Research Institute, Barcelona, Spain.
Universitat Pompeu Fabra, Barcelona, Spain.
Front Public Health. 2025 Jul 2;13:1548379. doi: 10.3389/fpubh.2025.1548379. eCollection 2025.
While there is wide evidence on concentrations of cytokines in patients attending health care facilities, evidence is scant on physiological, basal concentrations of cytokines in the general population and across sociodemographic groups, as well as on their potential stability over time. Furthermore, from a public health perspective it is remarkable that no studies have analyzed intraindividual changes in such concentrations from before the COVID-19 pandemic until its outbreak.
To investigate: (a) prepandemic concentrations of cytokines and immunoglobulins to viral exposures in a general, non-institutionalized population, and their associated sociodemographic variables; (b) the intraindividual change in such concentrations between a prepandemic period (2016-17) and the initial pandemic period (2020-21); and (c) whether such change was similar in participants who in 2020-21 were SARS-CoV-2 seronegative and seropositive, and between participants who did and did not develop COVID-19.
We conducted a prospective cohort study in 240 individuals from the general population of Barcelona, Spain. Thirty cytokines and 31 immunoglobulins were measured in paired serum samples collected in 2016-17 and 2020-21 in the same individuals.
The median value of the relative intraindividual change in cytokine concentrations between 2016 and 2020 was <15% for 29 of the 30 cytokines. A substantial number of participants had an intraindividual increase or decrease ≥15% in some cytokines. No major differences in intraindividual changes of cytokine and immunoglobulin levels between 2016 and 2020 were observed between participants who did and did not develop COVID-19.
We provide novel information on physiological, basal ex-vivo concentrations of cytokines and immunoglobulins in a general population, which should be relevant for clinical practice and public health. Intraindividual changes in cytokines and immunoglobulins during the 4 years from 2016-17 to 2020-21 were moderate, and they did not differ between participants who in 2020-21 were SARS-CoV-2 seropositive and seronegative, nor between participants who did and did not develop COVID-19 disease. These findings are also novel and relevant for medicine and public health. In particular, the stability in the biomarkers is relevant to assess the role of the immunological and inflammatory state (measured through baseline levels of cytokines and immunoglobulins) in the development of SARS-CoV-2 seropositivity and COVID-19 disease, as well as in the susceptibility to other infections and pathologies.
虽然有大量证据表明在医疗机构就诊的患者体内细胞因子的浓度情况，但关于普通人群以及不同社会人口学群体中细胞因子的生理基础浓度，以及它们随时间的潜在稳定性的证据却很少。此外，从公共卫生的角度来看，值得注意的是，尚无研究分析从新冠疫情大流行之前到疫情爆发期间这些浓度的个体内部变化。
调查：(a) 普通非机构化人群中细胞因子和免疫球蛋白对病毒暴露的疫情前浓度，以及它们相关的社会人口学变量；(b) 疫情前时期（2016 - 17年）和疫情初期（2020 - 21年）这些浓度的个体内部变化；以及(c) 在2020 - 21年期间新冠病毒血清阴性和血清阳性的参与者之间，以及感染和未感染新冠的参与者之间，这种变化是否相似。
我们对来自西班牙巴塞罗那普通人群的240名个体进行了一项前瞻性队列研究。在同一批个体于2016 - 17年和2020 - 21年采集的配对血清样本中，检测了30种细胞因子和31种免疫球蛋白。
30种细胞因子中有29种在2016年至2020年间个体内部细胞因子浓度相对变化的中位数<15%。相当数量的参与者在某些细胞因子上个体内部增加或减少≥15%。在感染和未感染新冠的参与者之间，未观察到2016年至2020年间细胞因子和免疫球蛋白水平个体内部变化的重大差异。
我们提供了关于普通人群中细胞因子和免疫球蛋白生理基础体外浓度的新信息，这对临床实践和公共卫生应该具有相关性。从2016 - 17年到2020 - 21年的4年期间，细胞因子和免疫球蛋白的个体内部变化较为适度，并且在2020 - 21年期间新冠病毒血清阳性和血清阴性的参与者之间，以及感染和未感染新冠疾病的参与者之间没有差异。这些发现对医学和公共卫生来说也是新颖且相关的。特别是，生物标志物的稳定性对于评估免疫和炎症状态（通过细胞因子和免疫球蛋白的基线水平来衡量）在新冠病毒血清阳性和新冠疾病发展中的作用，以及在对其他感染和疾病的易感性方面具有相关性。
