Age cohorts stratified according to age-distributions of COVID-19 morbidity statistics identify uniquely age-dependent CD3+CD8+ T-cell lymphocytopenia in COVID-19 patients without comorbidities on admission

Abstract

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=‒0.435, 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.

Keywords: C-reactive protein; CD8+ T cells; COVID-19; age-dependent immune features; coronavirus disease 2019.

Figure 1

The distribution of COVID-19 morbidities and disease severities in different age categories. (A) Detailed distributions of COVID-19 morbidities/age-year, (B, C) correlations between different age and COVID-19 cases/age-year, (D) mean values of COVID-19 cases/age-cohort, (E) COVID-19 incidence rate/age-cohort, and (F) disease severities in different age categories.

Figure 2

Blood lymphocyte and subset count, plasma C-reactive protein (CRP) and interleukin 6 (IL-6) levels in COVID-19 patients with different age categories. (A) Lymphocyte counts linearly decreased in the five age groups. (B) B cells did not significantly differ among the five age groups. (C) Natural killer (NK) cells did not differ among the five age groups. (D) Changes in T cell counts in the five age groups. (E) CD4⁺ T cells did not significantly differ among the five age groups. (F) CD8⁺ T cell counts linearly decreased in the five age groups. (G) Correlation between age and CD8⁺ T cell counts. (H) CRP levels linearly increased in the five age groups. (I) Changes in IL-6 levels in the five age groups. *p<0.05, **p<0.01, and ***p<0.001 vs. age group 2–25y; †p<0.05, ††p<0.01, and †††p<0.001 vs. age group 26–38y; and ǂ p<0.05 vs. age group 39–57y.