There were 163 participants enrolled with a median age of 87.3 years (IQR: 83.1–90.2 years), male of 88.3%, and being followed for a median of 156.4 weeks (IQR: 136.9-156.4 weeks). The physical function and cognitive status were relatively intact among participants, with median Barthel index score of 95 (IQR: 90–100) and Mini-Mental State Examination (MMSE) score of 26 (IQR: 23–29). Seropositivity was 99.4% of CMV (median IgG 236.8 IU/mL, IQR: 174.1- 722.1 IU/mL), 92% of VZV (median IgG 3.46 S/CO, IQR: 2.51–4.7 S/CO), 57.1% of HBV surface antigen (HBsAg) (median IgG 17 mIU/mL, IQR: 3.8–50.8 mIU/mL), 7.4% of HCV (median IgG 0.07 S/CO, IQR: 0.05–0.1 S/CO), and 84.7% of C. pneumoniae (median IgG 1.49 S/CO, IQR: 1.28–1.63 S/CO) respectively. Five 5 participants (3.1%) moved out the retirement communities without registration of final health outcome. The unexpected admission rate was 55.2% (31.9% by infectious disease, 6.7% by cardiovascular disease), and the 3-year mortality rate was 24.5% (9.2% by infectious diseases, 3.7% by cardiovascular disease). Demographic characteristics, chronic illness, geriatric syndromes, laboratory parameters in details were listed in Table 1.
Table 1
Baseline demographic characteristics of participants
Demographic and clinical characteristics | Participants N = 163 (100%) |
Age, years | 87.3 (83.1–90.2) |
Male gender (%) | 144 (88.3%) |
Follow-up duration, weeks | 156.4 (136.9- 156.4) |
Move out from retirement communities | 5 (3.1%) |
Unexpected admission rate (%) | 90 (55.2%) |
Infectious diseases-related (%) | 52 (31.9%) |
Cardiovascular diseases-related (%) | 11 (6.7%) |
Mortality rate (%) | 40 (24.5%) |
Infectious diseases-related (%) | 15 (9.2%) |
Cardiovascular diseases-related (%) | 6 (3.7%) |
Body mass index, kgs/m2 | 24.2 (21.1–26) |
Cigarette Smoking | |
Ex-smoker (%) | 17 (10.4%) |
Active smoker (%) | 20 (12.3%) |
Alcohol consumption | |
Ex-drinker (%) | 10 (6.1%) |
Active drinker (%) | 28 (17.2%) |
Education | |
< 6 years (%) | 53 (32.5%) |
6–9 years (%) | 51 (31.3%) |
> 9 years (%) | 48 (29.4%) |
Flu vaccine uptake (%) | 109 (66.9%) |
Underlying diseases | |
Cerebrovascular disease (%) | 9 (5.5%) |
Chronic liver disease (%) | 2 (1.2%) |
Chronic kidney disease (%) | 4 (2.5%) |
Chronic lung disease (%) | 24 (14.7%) |
Congestive heart failure (%) | 7 (4.3%) |
Dementia (%) | 7 (4.3%) |
Depression (%) | 8 (4.9%) |
Diabetes mellitus (%) | 45 (27.6%) |
Hypertension (%) | 118 (72.4%) |
Peptic ulcer disease (%) | 26 (16%) |
Peripheral arterial disease (%) | 32 (19.6%) |
Malignancy (%) | 11 (6.7%) |
Charlson comorbidity index | 1 (0–2) |
Geriatric syndromes | |
Physical function by BI score | 95 (90–100) |
Risk of falls by JHFRAT score | 12 (10–16) |
Polypharmacy (%) | 83 (50.9%) |
Types of medicine | 5 (3–6) |
Cognition by MMSE score | 26 (23–29) |
Depression by GDS-5 score | 0 (0–1) |
Malnutrition by MUST score | 0 (0–0) |
Visual impairment (%) | 52 (31.9%) |
Hearing impairment (%) | 27 (16.6%) |
Sleep disorder (%) | 46 (28.2%) |
Use of hypnotic agents (%) | 36 (22.1%) |
Constipation (%) | 44 (27%) |
Stool incontinence (%) | 3 (1.8%) |
Urinary incontinence (%) | 5 (3.1%) |
Laboratory tests | |
White blood cell count, cells/cumm | 5,900 (4,900- 6,700) |
Hemoglobin, gm/dL | 12.7 (11.6–13.6) |
Platelet count, x1,000 cells/cumm | 180.5 (148.7–221) |
Neutrophil count, cells/cumm | 3,157 (2,472- 3,914) |
Lymphocyte count, cells/cumm | 1,800 (1,500- 2,300) |
CD3+ T cell count, cells/cumm | 1,136 (903- 1,526) |
CD4+ T cell count, cells/cumm | 718 (557–926) |
CD8+ T cell count, cells/cumm | 390 (262–576) |
CD19+ B cell count, cells/cumm | 135 (81–205) |
CD4+/CD8+ | 1.81 (1.25–2.54) |
Albumin, gm/dL | 4 (3.8–4.2) |
Cholesterol, mg/dL | 163 (141–188) |
Triglyceride, mg/dL | 87 (62–122) |
HDL-C, mg/dL | 48 (36–57) |
LDL-C, mg/dL | 97 (77–117) |
BUN, mg/dL | 19.5 (16–25) |
Serum creatinine, mg/dL | 0.96 (0.79–1.24) |
Aspartate amonitransferase, U/L | 21 (17–25) |
hs-CRP, mg/dL | 0.14 (0.08–0.32) |
Lymphopenia (%) | 12 (7.4%) |
CD4+/CD8+ < 1 | 18 (11%) |
Chronic infection | |
CMV seropositivity (%) | 162 (99.4%) |
VZV seropositivity (%) | 150 (92%) |
HBsAg seropositivity (%) | 93 (57.1%) |
HCV seropositivity (%) | 12 (7.4%) |
Chlamydia pneumoniae seropositivity (%) | 138 (84.7%) |
CMV IgG, IU/mL | 236.8 (174.1- 722.1) |
VZV IgG, S/CO | 3.46 (2.51–4.7) |
HBsAg IgG, mIU/mL | 17 (3.8–50.8) |
HCV IgG, S/CO | 0.07 (0.05–0.1) |
Chlamydia pneumoniae IgG, S/CO | 1.49 (1.28–1.63) |
Abbreviations: BI: Barthel index; CD: cluster of differentiation; CMV: Cytomegalovirus; GDS-5: Geriatric Depression Scale-5 items; HBsAg: hepatitis B virus surface antigen; HCV: hepatitis C virus; HDL-C: high density lipoprotein-cholesterol; hs-CRP: highly sensitive C reactive protein; IgG: Immunoglobulin G; JHFRAT: John Hopkins Fall Risk Assessment Tool; LDL-C: Low density lipoprotein-cholesterol; MMSE: Mini-Mental Status Examination; MUST: Malnutrition Universal Screening Test; VZV: Varicella zoster virus |
In the Cox proportional hazards model, lymphopenia was shown an important predictor for both unexpected admission (OR: 2.97, 95% CI: 1.51–5.82) and mortality (OR: 2.32, 95% CI: 1- 5.33) in model 1, remained significant for unexpected admission (OR: 2.85, 95% CI: 1.2–6.74) but less significant for mortality (OR: 1.9, 95% CI: 0.66–5.4) in model 2. The 3rd quartile of CMV IgG (OR: 3.26, 95% CI: 1.55–5.2) and the 1st quartile of CD19+ B cell count (OR: 2.84, 95% CI: 1.29–6.25) indicated greater risk of unexpected admission, while the 3rd quartile of CD3+ T cell count had a reduced risk of mortality (OR: 0.19, 95% CI: 0.05–0.71) in model 2 (Table 2).
Table 2
The Cox proportional hazards model for mortality and unexpected admission
Variables | Unexpected admission: OR (95% CI) | Mortality: OR (95% CI) |
Unadjusted | Model 1 | Model 2 | Unadjusted | Model 1 | Model 2 |
CMV IgG, IU/mL |
< 174.1 | 1 | 1 | 1 | 1 | 1 | 1 |
174.1- 236.8 | 1.23 (0.63, 2.39) | 1.24 (0.62, 2.47) | 2.05 (0.93, 4.51) | 1.31 (0.52, 3.34) | 1.37 (0.53, 3.5) | 1.63 (0.57, 4.67) |
236.8- 722.1 | 2.56 (1.41, 4.64)** | 2.84 (1.56, 5.2)** | 3.26 (1.55, 6.84)** | 1.36 (0.54, 3.38) | 1.15 (0.45, 2.89) | 0.92 (0.31, 2.66) |
> 722.1 | 1.65 (0.88, 3.12) | 1.7 (0.89, 3.24) | 2.02 (0.97, 4.18) | 1.49 (0.6, 3.71) | 1.17 (0.46, 2.95) | 0.97 (0.35, 2.67) |
HCV IgG, S/CO |
< 0.0575 | 1 | 1 | 1 | 1 | 1 | 1 |
0.0575- 0.07 | 0.82 (0.45, 1.58) | 0.96 (0.51, 1.83) | 1.1 (0.5, 2.42) | 0.41 (0.17–0.97)* | 0.51 (0.21, 1.26) | 0.53 (0.18, 1.53) |
0.07–0.1 | 1.03 (0.55–1.91) | 1.39 (0.72, 2.67) | 1.62 (0.77, 3.39) | 0.58 (0.25, 1.32) | 0.85 (0.35, 2.06) | 0.95 (0.34, 2.58) |
> 0.1 | 1.63 (0.91, 2.91) | 1.71 (0.92, 3.18) | 1.84 (0.91, 3.72) | 0.53 (0.22, 1.26) | 0.65 (0.26, 1.59) | 0.65 (0.23, 1.81) |
Lymphopenia | 3.43 (1.8, 6.5)*** | 2.97 (1.51, 5.82)** | 2.85 (1.2, 6.74)** | 2.91 (1.29, 6.6)* | 2.32 (1, 5.33)* | 1.9 (0.66, 5.4) |
CD3+ T cell count, cells/cumm |
> 1,526 | 1 | 1 | 1 | 1 | 1 | 1 |
1,136- 1,526 | 0.97 (0.5, 1.88) | 0.77 (0.38, 1.53) | 0.43 (0.18, 1) | 0.43 (0.13, 1.4) | 0.21 (0.06, 0.73)* | 0.19 (0.05, 0.71)* |
903- 1,136 | 1.42 (0.77, 2.65) | 0.98 (0.49, 1.92) | 0.72 (0.34, 1.54) | 1.12 (0.45, 2.76) | 0.5 (0.19, 1.33) | 0.59 (0.2, 1.73) |
< 903 | 2.22 (1.23, 4.02)** | 1.54 (0.78, 3.03) | 1.04 (0.47, 2.28) | 2.07 (0.91, 4.7) | 1 (0.4, 2.47) | 0.94 (0.33, 2.7) |
CD4+ T cell count, cells/cumm |
> 926 | 1 | 1 | 1 | 1 | 1 | 1 |
557–718 | 1.34 (0.66, 2.69) | 1.06 (0.51, 2.22) | 0.63 (0.27, 1.46) | 1.45 (0.46, 4.58) | 1 (0.31, 3.18) | 0.95 (0.27, 3.38) |
718–926 | 2.15 (1.13, 4.11)* | 1.55 (0.77, 3.12) | 1.11 (0.52, 2.37) | 2.23 (0.77, 6.42) | 1.22 (0.42, 3.68) | 1.31 (0.41, 4.13) |
< 557 | 2.78 (1.46, 5.3)** | 1.75 (0.84, 3.67) | 1.57 (0.71, 3.46) | 3.88 (1.42, 10.61)** | 2.15 (0.75, 6.14) | 2.55 (0.8, 8.06) |
CD19+ B cell count, cells/cumm |
> 205 | 1 | 1 | 1 | 1 | 1 | 1 |
81–135 | 2.07 (1.06, 4.04)* | 1.76 (0.86, 3.6) | 1.59 (0.73, 3.46) | 1.46 (0.46, 4.62) | 0.97 (0.3, 3.12) | 0.99 (0.28, 3.5) |
135–205 | 1.54 (0.77, 3.08) | 1.24 (0.57, 2.71) | 1.05 (0.45, 2.48) | 2.42 (0.84, 6.98) | 1.35 (0.44, 4.12) | 1.11 (0.34, 3.64) |
< 81 | 3.1 (1.64, 5.84)*** | 2.24 (1.09, 4.63)* | 2.84 (1.29, 6.25)** | 3.67 (1.34, 10.03)* | 1.99 (0.68, 5.81) | 2.41 (0.79, 7.36) |
*p < 0.05, **p < 0.01, ***p < 0.001 |
Model 1: Adjusted by age, gender, body mass index, highly-sensitive C-reactive protein, and multimorbidity by Charlson comorbidity index |
Model 2: Adjusted by education status, cigarette smoking, alcohol consumption, albumin, low density lipoprotein cholesterol, medical history of acute myocardial ischemia, congestive heart failure, cerebrovascular accident, and diabetes mellitus, in addition to age, gender, body mass index, and multimorbidity |
The CMV IgG positively correlated with age, flu vaccine uptake, risks of fall, usage or hypnotic agents, C. pneumoniae IgG, while negatively associated with education, cognition, and CD19+ B cell count (Table 3). For all lymphocyte, CD3+ T cell, and CD19+ B cell counts, there were positive associations with female gender, body mass index (BMI), cognitive performance, hemoglobin, albumin, cholesterol, low density lipoprotein-cholesterol, while negative correlations with age and flu vaccine uptake. Other results of Spearman correlation analysis were listed in Table 3.
Table 3
Results of Spearman correlation analysis between baseline characteristics
Indicators | Variables | Correlation coefficient | p value |
CMV IgG | Age | 0.19 | 0.017* |
Education | -0.17 | 0.036* |
Flu vaccine uptake | 0.278 | 0.001** |
JHFRAT score | 0.219 | 0.006** |
MMSE score | -0.197 | 0.013* |
Usage of hypnotic agents | 0.169 | 0.043* |
CD19+ B cell count | -0.179 | 0.026* |
Chlamydia pneumoniae IgG | 0.194 | 0.015* |
Lymphocyte count | Age | -0.291 | < 0.001*** |
Female Gender | 0.226 | 0.004** |
Body mass index | 0.296 | < 0.001*** |
Flu vaccine uptake | -0.192 | 0.017* |
Smoking history | -0.194 | 0.014* |
Diabetes mellitus | 0.18 | 0.024* |
JHFRAT | -0.225 | 0.004** |
MMSE score | 0.227 | 0.004** |
MUST score | -0.259 | 0.001** |
White blood cell count | 0.5 | < 0.001*** |
Hemoglobin | 0.261 | 0.001** |
Platelet count | 0.185 | 0.018* |
CD3+ T cell count | 0.862 | < 0.001*** |
CD4+ T cell count | 0.757 | < 0.001*** |
CD8+ T cell count | 0.632 | < 0.001*** |
CD19+ B cell count | 0.449 | < 0.001*** |
Albumin | 0.297 | < 0.001*** |
Cholesterol | 0.319 | < 0.001*** |
Triglyceride | 0.177 | 0.024* |
LDL-C | 0.234 | 0.003** |
hs-CRP | -0.186 | 0.018* |
CD3+ T cell count | Age | -0.337 | < 0.001*** |
Female Gender | 0.304 | < 0.001*** |
Body mass index | 0.328 | < 0.001*** |
Flu vaccine uptake | -0.209 | 0.01* |
Diabetes mellitus | 0.195 | 0.015* |
JHFRAT score | -0.168 | 0.035* |
MMSE score | 0.193 | 0.015* |
MUST score | -0.224 | 0.005 |
White blood cell count | 0.401 | < 0.001*** |
Hemoglobin | 0.263 | 0.001** |
Platelet count | 0.17 | 0.032* |
Lymphocyte count | 0.862 | < 0.001*** |
CD4+ T cell count | 0.835 | < 0.001*** |
CD8+ T cell count | 0.792 | < 0.001*** |
CD19+ B cell count | 0.423 | < 0.001*** |
Albumin | 0.239 | 0.003** |
Cholesterol | 0.364 | < 0.001*** |
LDL-C | 0.281 | < 0.001*** |
Triglyceride | 0.206 | 0.01* |
Chlamydia pneumoniae IgG | -0.17 | 0.033* |
CD19+ B cell count | Age | -0.471 | < 0.001*** |
Female gender | 0.337 | < 0.001*** |
Body mass index | 0.265 | 0.001** |
Flu vaccine uptake | -0.278 | 0.001** |
Alcohol consumption | 0.215 | 0.007** |
Chronic liver disease | 0.184 | 0.02* |
Barthel index score | 0.23 | 0.004** |
MMSE score | 0.24 | 0.002** |
White blood cell count | 0.202 | 0.011* |
Hemoglobin | 0.232 | 0.003** |
Lymphocyte count | 0.449 | < 0.001*** |
CD3+ T cell count | 0.423 | < 0.001*** |
CD4+ T cell count | 0.587 | < 0.001*** |
CD4+/CD8+ | 0.343 | < 0.001*** |
Albumin | 0.192 | 0.016* |
Cholesterol | 0.299 | < 0.001*** |
LDL-C | 0.258 | 0.001** |
Creatinine | -0.168 | 0.035* |
CMV IgG | -0.179 | 0.026* |
*p < 0.05, **p < 0.01, ***p < 0.001 |
Abbreviations: CD: cluster of differentiation; CMV: cytomegalovirus; HDL-C: high density lipoprotein-cholesterol; hs-CRP: highly sensitive C reactive protein; IgG: Immunoglobulin G; JHFRAT: John Hopkins Fall Risk Assessment Tool; LDL-C: Low density lipoprotein-cholesterol; MMSE: Mini-Mental Status Examination; MUST: Malnutrition Universal Screening Test; VZV: Varicella zoster virus |
Additional adjustment for associating factors was performed in final model and still reported an elevated risk of unexpected admission for the 3rd quartile of CMV IgG (OR: 2.66, 95% CI: 1.14–6.2). With adjustment for correlating factors after removing white blood cell count, lymphocyte and subset counts, lymphopenia still indicated an increased risk of unexpected admission (OR: 3.59, 95% CI: 1.34–9.59), and the 3rd quartile of CD3+ T cell remained a reduced risk of mortality (OR: 0.38, 95% CI: 0.15–0.95).