Immune cell population and cytokine profiling suggest age dependent differences in the response to SARS-CoV-2 infection

Abstract

Aging population is at higher risk of developing severe COVID-19, including hospitalization and death. In this work, to further understand the relationship between host age-related factors, immunosenescence/exhaustion of the immune system and the response to the virus, we characterized immune cell and cytokine responses in 58 COVID-19 patients admitted to the hospital and 40 healthy controls of different age ranges. Lymphocyte populations and inflammatory profiles were studied in blood samples, using different panels of multicolor flow cytometry. As expected, our analysis reveals differences at both the cellular and cytokine level in COVID-19 patients. Interestingly, when the age range analysis was carried out, the immunological response to the infection was found to differ with age, being especially affected in the group of 30-39 years. In this age range, an increased exhausted T cell response and a decrease of naïve T helper lymphocytes was found in patients, as well as a reduced concentration of the proinflammatory TNF, IL-1β and IL-8 cytokines. Besides, the correlation between age and the study variables was evaluated, and multiple cell types and interleukins were found to correlate with donor age. Notably, the correlations of T helper naïve and effector memory cells, T helper 1-17 cells, TNF, IL-10, IL-1β, IL-8, among others, showed differences between healthy controls and COVID-19 patients. Our findings, in the context of other previous studies, suggest that aging affects the behavior of the immune system in COVID-19 patients. They suggest that young individuals are able to mount an initial response to SARS-CoV-2, but some of them present an accelerated exhaustion of the cell response and an insufficient inflammatory response, resulting in a moderate to severe COVID-19. On the other hand, in older patients there is a smaller immune cell response to the virus, reflected in fewer differences in immune populations between COVID-19 patients and controls. Nevertheless, old patients show more evidence of an inflammatory phenotype, suggesting that the underlying inflammation associated with their age is exacerbated by the SARS-CoV-2 infection.

Keywords: COVID-19; SARS-CoV-2; Severe COVID-19; immunosenescence and exhaustion; immunosenescence and inflammaging.

FIGURE 1

Variables found to be significantly different in COVID-19 patients with respect to healthy controls (HCs). (A) Leukocytes percentage, (B) T lymphocytes percentage, (C) Th2 lymphocytes percentage, (D) Th17 lymphocytes percentage, (E) T regulatory lymphocytes percentage, (F) Exhausted Th lymphocytes percentage, (G) Exhausted Tc-lymphocytes percentage, (H) B lymphocytes percentage, (I) TNF concentration and (J) IL-1β concentration. The statistical significance is depicted with asterisk code meaning: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.

FIGURE 2

Correlation between immune variables and age. (A) Naïve Th lymphocytes percentage, (B) Effector memory Th lymphocytes percentage, (C) Tc lymphocytes percentage, (D) Th1-17 lymphocytes percentage, (E) Naïve Tc lymphocytes percentage, (F) Central memory Tc lymphocytes percentage, (G) TNF concentration, (H) IL-10 concentration, (I) IL-1β concentration and (J) IL-8 concentration. Pearson and Spearman tests were used for normally and non-normally distributed variables, respectively. Significant results are underlined.

FIGURE 3

Variables found to be significantly different in COVID-19 patients with respect to healthy controls analyzed by age ranges. (A) Significantly different variables in the age range from 30 to 39 years old. (B) Significantly different variables in the age range from 40 to 49 years old. (C) Significantly different variables in the age range from 50 to 59 years old. (D) Significantly different variables in the age range from 60 to 69 years old. The statistical significance is depicted with asterisk code meaning: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.