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Aging and disease    2020, Vol. 11 Issue (3) : 642-648     DOI: 10.14336/AD.2020.0317
Orginal Article |
Immune Characteristics of Patients with Coronavirus Disease 2019 (COVID-19)
Xiaotian Dong1, Mengyan Wang2, Shuangchun Liu1, Jiaqi Zhu1, Yanping Xu3, Hongcui Cao3,4,5,*, Lanjuan Li3,4
1Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
2Department of Infectious Diseases, Xixi Hospital of Hangzhou, Hangzhou, China.
3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
4National Clinical Research Center for Infectious Diseases, Hangzhou, China.
5Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, Hangzhou, China
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Abstract  

Up to now, little is known about the detailed immune profiles of COVID-19 patients from admission to discharge. In this study we retrospectively reviewed the clinical and laboratory characteristics of 18 COVID-19 patients from January 30, 2020 to February 21, 2020. These patients were divided into two groups; group 1 had a severe acute respiratory syndrome coronavirus 2 nucleic acid-positive duration for more than 15 days (n = 6) and group 2 had a nucleic acid-positive duration for less than 15 days (n = 12). Group 1 patients had lower level of peripheral blood lymphocytes (0.40 vs. 0.78 ×109/L, p = 0.024) and serum potassium (3.36 vs. 3.79 mmol/L, p = 0.043) on admission but longer hospitalization days (23.17 vs. 15.75 days, p < 0.001) compared to Group 2 patients. Moreover, baseline level of lymphocytes (r = -0.62, p = 0.006) was negatively correlated with the nucleic acid-positive duration. Additionally, lymphocytes (420.83 vs. 1100.56 /μL), T cells (232.50 vs. 706.78 /μL), CD4+ T cells (114.67 vs. 410.44 /μL), and CD8+ T cells (94.83 vs. 257.44 /μL) in the peripheral blood analyzed by flow cytometry were significantly different between Group 1and Group 2. Furthermore, there was also a negative correlation between lymphocytes (r = -0.54, p = 0.038) or T cells (r = -0.55, p = 0.034) at diagnosis and the nucleic acid-positive duration, separately. In conclusion, the patients with nucleic acid-positive ≥ 15 days had significantly decreased lymphocytes, T cell and its subsets compared to those who remained positive for less than 15 days.

Keywords coronavirus disease 2019 (COVID-19)      immune characteristics      lymphocyte subsets      serum potassium     
Corresponding Authors: Cao Hongcui   
About author:

These authors contributed equally to this work.

Just Accepted Date: 19 March 2020   Online First Date: 20 March 2020    Issue Date: 13 May 2020
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Dong Xiaotian
Wang Mengyan
Liu Shuangchun
Zhu Jiaqi
Xu Yanping
Cao Hongcui
Li Lanjuan
Cite this article:   
Dong Xiaotian,Wang Mengyan,Liu Shuangchun, et al. Immune Characteristics of Patients with Coronavirus Disease 2019 (COVID-19)[J]. Aging and disease, 2020, 11(3): 642-648.
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http://www.aginganddisease.org/EN/10.14336/AD.2020.0317     OR
CharacteristicsCOVID-19 patients
(n = 18)
Nucleic acid-positive <15 days
(n = 12)
Nucleic acid-positive≥15 days
(n = 6)
p value1
Age (years)58.39 ± 17.2156.50 ± 16.5462.17 ± 19.470.527
Male, no. (%)11 (61.11)7 (58.33)4 (66.67)1.000
Hospitalization days18.22 ± 4.8615.75 ± 3.5523.17 ± 2.93<0.001*
SARS-CoV-2 nucleic acid-positive duration (day)11.89 ± 7.287.50 ± 3.4020.67 ± 4.03<0.001*
Laboratory data
Activated partial thromboplastin time (sec)31.55 ± 6.0430.68 ± 3.3433.30 ± 9.700.401
International normalized ratio0.99 ± 0.100.97 ± 0.061.05 ± 0.150.130
Prothrombin time (sec)11.92 ± 1.2011.62 ± 0.7212.53 ± 1.760.130
D-dimer (μg/L)877.56 ± 983.70948.25 ± 1090.61798.34 ± 325.920.680
White blood cell (109/L)9.17 ± 5.249.29 ± 5.218.93 ± 5.800.896
Neutrophils (109/L)8.16 ± 5.148.08 ± 5.218.30 ± 5.480.936
Lymphocytes (109/L)0.66 ± 0.460.78 ± 0.490.40 ± 0.270.024*
Hemoglobin (g/L)131.17 ± 16.38134.33 ± 15.95124.83 ± 16.730.258
Monocytes (109/L)0.33 ± 0.230.39 ± 0.250.22 ± 0.100.144
Procalcitonin (ng/mL)0.09 ± 0.090.09 ± 0.090.10 ± 0.090.899
Lactate dehydrogenase (U/L)317.78 ± 136.18305.42 ± 76.46342.50 ± 221.570.601
Total bilirubin (μmol/L)13.16 ± 7.5611.94 ± 7.5215.58 ± 7.700.351
Alanine aminotransferase (U/L)25.22 ± 13.5227.00 ± 13.7121.67 ± 13.600.447
Albumin (g/L)37.61 ± 5.0038.55 ± 5.6635.72 ± 2.820.269
Glutamyl transpeptidase (U/L)45.78 ± 32.4343.58 ± 24.9950.17 ± 46.550.697
Alkaline phosphatase (U/L)76.00 ± 31.6081.42 ± 34.4865.17 ± 23.860.318
Creatinine (μmol/L)86.83 ± 67.2594.08 ± 81.2472.33 ± 21.910.534
Aspartate aminotransferase (U/L)26.56 ± 14.0226.17 ± 10.0527.33 ± 21.090.874
C reactive protein (mg/L)36.70 ± 44.0228.68 ± 38.6152.74 ± 53.330.288
Blood lactic acid (mmol/L)2.13 ± 0.942.14 ± 1.162.10 ± 0.300.933
Partial pressure of oxygen (mmHg)96.55 ± 47.30108.66 ± 50.3772.33 ± 31.140.128
Oxygen saturation (%)94.35 ± 7.0796.51 ± 2.7390.03 ± 10.950.210
Hematocrit (%)41.76 ± 7.5742.02 ± 6.9041.25 ± 9.480.847
Potassium (mmol/L)3.65 ± 0.443.79 ± 0.333.36 ± 0.520.043*
Sodium (mmol/L)138.11 ± 10.44139.75 ± 3.79134.83 ± 17.870.533
Creatine kinase (U/L)22.33 ± 7.6822.25 ± 8.5722.50 ± 6.220.950
Table 1  Characteristics of COVID-19 patients on admission.
Figure 1.  Correlation analysis between lymphocytes count and the duration of nucleic acid-positive of COVID-19 patients. Lymphocytes count in peripheral blood (A) but not serum potassium level (B) at admission was negatively correlated with the SARS-CoV-2 nucleic acid-positive duration. Spearman correlation analysis was performed. p<0.05 as statistical significance.
CytokinesNormal rangeCOVID-19 patients (n = 17)Nucleic acid-positive < 15 days (n = 11)Nucleic acid-positive ≥ 15 days (n = 6)p value1
IFN-γ (pg/mL)0.00-20.0613.08 ± 15.969.06 ± 8.6920.45 ± 23.750.302
IL-10 (pg/mL)0.00-2.315.83 ± 4.914.15 ± 3.298.92 ± 6.140.052
IL-2 (pg/mL)0.00-4.131.26 ± 0.551.08 ± 0.361.6 ± 0.710.143
IL-4 (pg/mL)0.00-8.372.05 ± 1.931.50 ± 0.243.05 ± 3.140.281
IL-6 (pg/mL)0.00-6.6129.51 ± 19.1023.82 ± 15.3839.94 ± 22.200.097
TNF-α (pg/mL)0.00-33.2738.44 ± 41.4622.49 ± 20.9267.69 ± 55.140.103
Table 2  Characteristics of serum cytokines of COVID-19 patients at diagnosis.
Lymphocyte subsetsNormal rangeCOVID-19 patients (n = 15)Nucleic acid-positive < 15 days (n = 9)Nucleic acid-positive ≥ 15 days (n = 6)p value
At diagnosisAt discharge1At diagnosisAt discharge2At diagnosisAt discharge3
Lymphocytes (/μL)1530-3700828.67 ± 700.991301.53 ± 566.77*1100.56 ± 784.761372.89 ± 558.81420.83 ± 240.611194.50 ± 613.92*0.035*
T cells (/μL)955-2860517.07 ± 496.82906.87 ± 412.71*706.78 ± 567.01949.44 ± 424.35232.50 ± 121.53843.00 ± 425.02*0.038*
CD3+CD4+CD8- T cells (/μL)550-1440292.13 ± 323.05524.07 ± 294.16*410.44 ± 375.48548.67 ± 332.58114.67 ± 60.32487.17 ± 250.17*0.047*
CD3+CD4-CD8+ T cells (/μL)320-1250192.40 ± 170.89324.53 ± 186.26*257.44 ± 191.84339.33 ± 147.9594.83 ± 62.08302.33 ± 247.240.039*
CD4+/CD8+ ratio0.71-2.781.69 ± 1.112.05 ± 1.181.81 ± 1.271.86 ± 1.131.51 ± 0.902.32 ± 1.300.629
B cells (/μL)90-560168.40 ± 135.75221.73 ± 111.09*219.44 ± 148.39226.44 ± 131.0691.83 ± 68.10214.67 ± 83.52*0.072
NK cells (/μL)150-1100120.13 ± 82.92140.93 ± 123.40148.56 ± 91.59179.78 ± 118.7177.50 ± 46.8282.67 ± 115.310.106
Table 3  Lymphocyte subsets in COVID-19 patients at diagnosis and at discharge.
Figure 2.  Correlation analysis between lymphocyte subset numbers and the nucleic acid-positive duration of COVID-19 patients. Lymphocytes count in peripheral blood (A) and T cells (B) at diagnosis were negatively correlated with the duration of SARS-CoV-2 nucleic acid-positive. CD4+ T cells (C) and CD8+ T cells (D) were not correlated with the duration of SARS-CoV-2 nucleic acid-positive. Spearman correlation analysis was performed. p<0.05 as statistical significance.
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