Valiathan et al., 2016 (1), published an informative article on the aging of the immune system. The authors found that lymphocytes in the elderly, 70 to 92 years, were lower than in adults, 21 to 50 years. Neutrophils in the elderly were elevated. Cytokine IL-6 was also elevated in the elderly. Levels of lymphocytes, neutrophils, and IL-6 all have strong predictive value in the outcome of COVID-19.
Herold and colleagues, 2020 (2), showed that IL-6 at admission is predictive of progression to respiratory distress in COVID-19 patients. Above 80 pg/mL the predictive value for intubation was 92%.
From another article on this website:
Reduced lymphocytes counts and increased neutrophils to lymphocytes ratio (NLR) is a prominent feature of COVID-19. Higher NLRs are associated with poor outcomes.
With age, the immune system becomes senescent. From another article on this website:
The senescent immune system displays reduced responsiveness, and this has to be overcome if therapeutic vaccination is to be of benefit for the patient. Although the defects are quite well-characterized, the molecular mechanisms, inducing and sustaining immunosenescence and ways to overcome them, are still to be explored in more detail.
Given the above, it is interesting to learn how the levels of different elements involved in the immune response evolve throughout lifetime. Valiathan et al., 2016 (1), presented their relevant findings in a series of informative graphs that we share below.
Figure 1
Values of CBC parameters; WBC, RBCs, Haemoglobin, HCT, MCV, MCHC and MCH in participants of different age groups: Complete blood cell counts was performed on the day of specimen collection using Coulter AcT5 differential haematology analyser (Beckman Coulter, Fullerton, CA). Group 1: infants (Gr1, n = 35), Group 2: Children (Gr2, n = 27), Group 3: Adolescents (Gr3, n = 36), Group 4: Adults (Gr4, n = 60) and Group 5: Elderly (Gr5, n = 33). Values of the CBC parameters like WBC, RBCs, haemoglobin, HCT, MCV, MCHC and MCH for the five group studied showed differences mainly between the first three groups (infants versus children and children versus adolescents and infants versus adolescents. Graphical plot represents mean with standard deviation for different CBC components: (A) WBC (cells/μl), (B) RBCs (million/mm3), (C) Haemoglobin (g/dl), (D) HCT (%), (E) MCV (fL), (F) MCHC (g/dl) and (G) MCH (pg).
Source: Valiathan, 2016. Figure 2
Differences in parameters like lymphocytes, monocytes, neutrophils, eosinophils and basophils and platelet counts during ageing: The neutrophils increased continuously with age while platelet counts and basophils decreased with age. Group1: Infants (Gr1, n = 28), Group 2: Children (Gr2, n = 21), Group 3: Adolescents (Gr3, n = 36), Group 4: Adults (Gr4, n = 47) and Group 5: Elderly (Gr5, n = 29). Graphical plot represents mean with standard deviation: (A) Lymphocytes, (B) Monocytes, (C) Neutrophils (%), (D) Eosinophils (%), (E) Basophils (%) and (F) Platelet count/mm3.
Source: Valiathan, 2016.Figure 3
Comparison of lymphocyte subset percentages between different groups: Flow cytometric enumeration of T, B and NK cells was performed. Absolute lymphocyte counts were determined as the product of the WBC count and percent lymphocyte differential as measured by the Coulter AcT5 differential haematology analyser. We performed five different comparisons: infants with children, children with adolescents, adolescents with adults, adults with elderly and adolescents with elderly. Group 1: Infants (Gr1, n = 35), Group 2: Children (Gr2, n = 27), Group 3: Adolescents (Gr3, n = 36), Group 4: Adults (Gr4, n = 60) and Group 5: (Gr5, n = 33). Graphical plot represents mean percentage with standard deviation for the five study groups. (A) CD3 (%), (B) CD4 (%), (C) CD8 (%), (D) CD19 (%) and (E) CD56+16+ (%).
Source: Valiathan, 2016.Figure 4
Correlation of various lymphocyte subset percentages with age in different study groups: We performed correlation analysis of various lymphocyte subset percentages with age. The graph shows the correlation of age with different lymphocyte subsets: (A) CD3+ (%), (B) CD4+ (%), (C) CD8+ (%), (D) CD19 (%) and (E) CD56+CD16+ (%).
Source: Valiathan, 2016.Figure 5
Differences in CBC parameters (Lymphocytes, Monocytes, Neutrophils, Eosinophils, Basophils and Platelet Count) based on gender: Graphical plot represents mean values with standard deviation of the five study groups for different CBC components: (A) Lymphocytes, (B) Monocytes, (C) Neutrophils (%), (D) Eosinophils (%), (E) Basophils (%) and (F) Platelet count/mm3. Infants (Female, n = 14; Male, n = 14), Child (Female, n = 11; Male, n = 10), Adolescent (Female, n = 18; Male, n = 18), Adult (Female, n = 25; Male, n = 22) and Elderly (Female, n = 22; Male, n = 7). ϕ statistically significant difference.
Source: Valiathan, 2016.Figure 6
Differences in lymphocyte subsets in females and males in the different study groups: Graphical plot represents mean values with standard deviation of different lymphocyte subsets for the males and females of the five study groups. (A) CD3 (%), (B) CD4 (%), (C) CD8 (%), (D) CD19 (%) and (E) CD56+16+ (%). Infant (Female, n = 17; Male, n = 18), Child (Female, n = 14; Male, n = 13), Adolescent (Female, n = 18; Male, n = 18), Adult (Female, n = 29; Male, n = 31) and Elderly (Female, n = 25; Male, n = 8).
Source: Valiathan, 2016.Figure 7 Plasma cytokine and growth factor levels in adults and elderly: Cytokine levels in plasma specimens of adults and elderly were measured using a multiplex biochip array system, Evidence Investigator TM (Randox laboratories Ltd, Crumlin, UK). The bar diagram shows mean with standard error of mean for: (A) TH-1 Cytokines [IL-2, IL-8, IL-1a, IL-1b, IFN-c and TNF-a], (B) TH-2 Cytokines [IL-4, IL-6 and IL-10] and (C) Growth Factors (MCP-1, VEGF and EGF). Significant differences were observed in the concentration of plasma levels of IL-1b, IL-2, IFN-c, TNF-a, IL-6, MCP-1 and EGF between the elderly participants and adults. Source: Valiathan, 2016.
For comparison, we insert below a table with characteristics of COVID-19 patients from a study from China (3). You can see that in COVID-19 patients with a mostly mild and moderate course of COVID-19, IL-6 levels are comparable to the levels recorded by Valiathan et al., 2016 (1), in the elderly.
A focus on TNF-alpha, IL-6 and several other markers at baseline. Source: Tang, 2020.Table 1 | Baseline demographic and clinical characteristics of patients in intention to treat population. Values are
numbers (percentages) unless stated otherwise.
Source: Tang, 2020.
covid-19=coronavirus disease 2019; HCQ=hydroxychloroquine; SOC=standard of care.
To convert values for creatinine to mg/dL, divide by 88.4. To convert values for total bilirubin to mg/dL, divide by 17.1.
*Weight in kilograms divided by square of height in metres.
The citation below explains how Valiathan et al., 2016 (1), obtained their data:
Subjects and samples. This study was conducted at the University of Miami-Miller School of Medicine by retrospectively analysing the data for complete blood count (CBC) components and circulating lymphocyte subsets from infant to elderly age groups to determine the changes as well as differences in these parameters. The protocols involving human subjects were approved by Institutional Review Board prior to conducting the research. The study was conducted on peripheral blood specimens from Group 1 (Gr1): infants (1 month to 7 months, n = 35), Group 2 (Gr2): children (1 year to 6 years, n = 27), Group 3 (Gr3): adolescents (12 years to 18 years, n = 36), Group 4 (Gr4): adults (21 years to 50 years, n = 60) and Group 5 (Gr5): elderly (70 years to 92 years, n = 33). The numbers of males and females were: infants (males: 18 and females: 17), children (males: 13 and females: 14), adolescents (males: 19 and females: 17), adults (males: 31 and females: 29) and elderly (males: 8 and females: 25). The age ranges for different study groups were derived based on previous reports [40–42]. All the participants were in good health without any pre-existing medical conditions and all adolescents, adults and elderly participants were non-smokers.
Selected references:
1. Valiathan et al. Scandinavian Journal of Immunology, 2016, 83, 255–266.
2. Herold T, Jurinovic V, Arnreich C, Hellmuth JC, von Bergwelt-Baildon M, Klein M, Weinberger T. Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients. medRxiv 2020.04.01.20047381; doi: https://doi.org/10.1101/2020.04.01.20047381.
3. Tang Wei, Cao Zhujun, Han Mingfeng, Wang Zhengyan, Chen Junwen, Sun Wenjin et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial BMJ 2020; 369 :m1849
![Figure 7 Plasma cytokine and growth factor levels in adults and elderly: Cytokine levels in plasma specimens of adults and elderly were measured using a multiplex biochip array system, Evidence Investigator TM (Randox laboratories Ltd, Crumlin, UK). The bar diagram shows mean with standard error of mean for: (A) TH-1 Cytokines [IL-2, IL-8, IL-1a, IL-1b, IFN-c and TNF-a], (B) TH-2 Cytokines [IL-4, IL-6 and IL-10] and (C) Growth Factors (MCP-1, VEGF and EGF). Significant differences were observed in the concentration of plasma levels of IL-1b, IL-2, IFN-c, TNF-a, IL-6, MCP-1 and EGF between the elderly participants and adults. Source: Valiathan, 2016.](https://medical-en.nneandersphysiologicalliteracy.com/wp-content/uploads/2020/05/Foxit-PhantomPDF_2020-05-16_13-44-39.jpg)
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