Characterizing distinct profiles of immune and inflammatory response with age to Omicron infection

Abstract

Background: Understanding inflammatory and immune responses to Omicron infection based on age is crucial when addressing this global health threat. However, the lacking of comprehensive elucidation hinders the development of distinct treatments tailored to different age populations.

Methods: 1299 cases of Omicron infection in Shanghai were enrolled between April 10, 2022 and June 3, 2022, dividing into three groups by ages: Adult group (18-59 years), Old group (60-79 years), and Elder group (≥ 80 years). Laboratory data including inflammatory cytokines, cellular, and humoral immunity were collected and analyzed.

Results: The mean age of Adult, Old, and Elder groups were 44.14, 69.98, and 89.35 years, respectively, with 40.9% being men. The Elder group patients exhibited higher white blood cell (WBC) counts and elevated levels of inflammatory cytokines, but their lymphocyte counts were relatively lower. In comparison to the Old group patients, the Elder group patients demonstrated significantly lower CD3⁺ T-cell counts, CD3⁺ T-cell proportion, CD4⁺ T-cell counts, CD8⁺ T-cell counts, and CD19⁺ B-cell counts, while the NK-cell counts were higher. Omicron negative patients displayed a higher proportion of CD19⁺ B-cells and higher levels of Complement-3 and IL-17 compared to the positive patients in the Old group. Omicron negative patients had lower WBC counts, CD3⁺CD8⁺ T-cells proportion, and the levels of serum amyloid A and IgA in the Elder group, but the CD4⁺/CD8⁺ ratio was higher.

Conclusions: Our study identified the distinct profiles of inflammatory and immune responses to Omicron infection varying with age and highlighted the diverse correlations between the levels of various biomarkers and Omicron infected/convalescent patients.

Keywords: COVID-19; age; immunology; inflammation; omicron.

Figure 1

Demographic characteristics and laboratory findings of Omicron infection patients at study entry. (A) The mean age of the Adult, Old, and Elder groups were 44.14 ± 10.26 years (n = 382), 69.98 ± 5.34 years (n = 445), and 89.35 ± 4.93 years (n = 472). (B) The Elder group had higher WBC counts than the Adult group. (C) The Elder group had the highest neutrophils count compared with the Adult and Old groups. (D) The Adult group had higher platelet counts compared with the Elder group. (E) The lymphocyte count for the Elder group were lower than the Adult and Old groups. (F) The levels of hemoglobin for the Elder group were lower than the Adult and Old groups. (G) The levels of total protein for the Elder group were lower than the Adult and Old groups. (H) The levels of albumin for the Elder group were lower than the Adult and Old groups. (I) The Adult group had higher levels of ALT than the Elder group, but the Old group had lower levels of ALT than the Elder group. (J) The Elder group had higher levels of total bilirubin than the Adult group (K) The Elder group had the highest levels of direct bilirubin compared with the Adult and Old group. (L) There were no significant differences in the AST levels among the three groups. (M) There were no significant differences in the γ-glutamyltransferase levels among the three groups. (N) The Adult group had higher levels of serum creatinine than the Elder group, but the Old group had lower levels of ALT than the Elder group. (O) The levels of blood urea nitrogen was the highest in the Elder group. (P) CRP levels were higher in the Elder group than the Adult and Old group. (Q) IL-6 levels were higher in the Elder group than the Adult and Old group. (R) SAA levels were higher in the Elder group than the Adult and Old group. (S) PCT levels were higher in the Elder group than the Adult and Old group. In figure (B–O), 99 individuals were tested in the Adult group, 251 individuals in the Old group, and 308 individuals in the Elder group. In figure (P–S), 54 individuals were tested in the Adult group, 156 individuals in the Old group, and 186 individuals in the Elder group. Data were shown as mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001; WBC, white blood cell; PLT, platelet; Hb, hemoglobin; TP, total protein; ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; TB, total bilirubin; DB, direct bilirubin; γ-GT, γ-Glutamyltransferase; Cr, serum creatinine; BUN, blood urea nitrogen; CRP, C-reactive protein; IL-6, interleukin-6; SAA, serum amyloid A; PCT, procalcitonin.

Figure 2

(A) The days taken for the Omicron infection patients turning negative for the Adult group (4.91 ± 3.67 days, n = 212) was significantly shorter than the Old and Elder groups (6.16 ± 4.63 days, n = 376; 6.8 ± 5.70 days, n = 415). (B) The change of the mean Ct value of ORF gene in different age groups during hospitalization. (C) The change of the mean Ct value of N gene in different age groups during hospitalization. The mean Ct value of ORF and N genes exhibited a rapid change after hospitalization in the Adult group, whereas the change of Ct value was much slower in the Old and Elder group. Data were shown as mean ± SD. **P < 0.01 and ***P < 0.001. Bule line represents Adult group, green line represents Old group, and Orange line represents Elder group. Red dot line represents Ct value of 35.

Figure 3

The characteristic change for white blood cell, lymphocyte, and inflammatory cytokines in different age during hospitalization. (A) Compared with the Elder group, total WBC counts were lower in the Adult group at Day 1 and Day 5 after hospitalization. (B) The total lymphocyte counts of the Adult and Old groups were higher than the Elder group at Day 1. At Day 7, the lymphocyte counts were higher in the Adult group than the Old and Elder groups. The temporal change patterns varied for the inflammatory cytokines levels. (C) CPR levels were higher in the Elder group than the Adult and Old group at Day 1. (D) IL-6 levels were higher in the Elder group than the Adult and Old group at Day 1. (E) SAA levels were higher in the Elder group than the Adult and Old group at Day 1. (F) PCT levels were higher in the Elder group than the Adult and Old group at Day 1. In figure (A, B), 99 individuals were tested in the Adult group, 251 individuals in the Old group, and 308 individuals in the Elder group at day 1; 26 individuals were tested in the Adult group, 85 individuals in the Old group, and 149 individuals in the Elder group at day 5; 27 individuals were tested in the Adult group, 80 individuals in the Old group, and 188 individuals in the Elder group at day 7; 11 individuals were tested in the Adult group, 54 individuals in the Old group, and 115 individuals in the Elder group at discharge. In figure (C–F), 54 individuals were tested in the Adult group, 156 individuals in the Old group, and 186 individuals in the Elder group at day 1; 4 individuals were tested in the Adult group, 22 individuals in the Old group, and 39 individuals in the Elder group at day 5; 23 individuals were tested in the Old group and 35 individuals in the Elder group at day 7; 26 individuals were tested in the Old group and 48 individuals in the Elder group at discharge. Data were shown as mean ± SE. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001; WBC, white blood cell; CRP, C-reactive protein; IL-6, interleukin-6; SAA, serum amyloid A; PCT, procalcitonin.

Figure 4

The characteristic change for novel immune and inflammatory markers in different age during hospitalization. (A) The Old group had higher CD3⁺ T counts than the Elder group at Day 3 and Day 7. (B) The proportion of CD3⁺ T in the Old group was higher than the Elder group at Day 7. (C) The counts of CD4⁺ T in the Old group were higher than the Elder group at Day 7. (D) The CD8⁺ T counts in the Old group were higher than the Elder group at Day 7. (E) The Old group had higher CD⁺ 19 B cell counts than the Elder group at day 3 and Day 7. (F) The NK proportion was lower in the Old group compared with the Elder group at Day 7. (G) The C3 levels were higher in the Old group than the Elder group at Day 7. (H) IL-5 levels in the Old group were higher than the Elder group at discharge. 24 individuals were tested in the Old group and 28 individuals in the Elder group at day 3; 26 individuals were tested in the Old group and 31 individuals in the Elder group at day 7; 19 individuals were tested in the Old group and 27 individuals in the Elder group at discharge. Data were shown as mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. NK, nature kill cell; C3, complement 3; IL-5, interleukin 5.

Figure 5

The correlation between Omicron infected/convalescent patients and immunological and inflammatory cytokines in different age population. (A) In the Elder group, the WBC counts in the positive patients were higher compared with the negative patients. (B) SAA levels in the positive patients were higher compared with the negative patients in the Elder group. (C) The positive patients in the Elder group had higher CD3⁺CD8⁺ proportion than the negative patients. (D) The ratio of CD4⁺/CD8⁺ was lower in the positive patients of the Elder group than the the negative patients. (E) The CD19⁺ proportion in the negative patients of the Old group was higher than the the positive patients. (F) The negative patients had higher levels of C3 compared with the positive patients in the Old group. (G) The IgA levels in the negative patients of the Elder group was lower than the positive patients. (H) IL-17 levels in the negative patients of the Old group was higher than the positive patients. Data were shown as mean ± SE. *P < 0.05. WBC, white blood cell; SAA, serum amyloid A; C3, complement 3; IL-17, interleukin 17.