Stability of cytokine and immunoglobulin concentrations in the general population: prepandemic basal concentrations and intraindividual changes until the COVID-19 pandemic.

Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.