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Front. Med.    2022, Vol. 16 Issue (1) : 111-125    https://doi.org/10.1007/s11684-021-0854-5
RESEARCH ARTICLE
Clinical characteristics and risk factors of COVID-19 patients with chronic hepatitis B: a multi-center retrospective cohort study
Jing Wang1, Zequn Lu2, Meng Jin3, Ying Wang4, Kunming Tian5,6, Jun Xiao1, Yimin Cai2, Yanan Wang1, Xu Zhang7, Tao Chen8, Zhi Yao9, Chunguang Yang1, Renli Deng10, Qiang Zhong11, Xiongbo Deng12, Xin Chen13, Xiang-ping Yang14, Gonghong Wei15, Zhihua Wang1(), Jianbo Tian2(), Xiao-ping Chen16()
1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2. Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
3. Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China
4. Department of Virology, Wuhan Centers for Disease Prevention and Control, Wuhan 430024, China
5. Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
6. School of Nursing, Zunyi Medical University, Zunyi 563099, China
7. Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
8. Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
9. Department of Respirology and Tuberculosis Specialty, Wuhan Pulmonary Hospital, Wuhan 430030, China
10. The Fifth Affiliated (Zhuhai) Hospital of Zunyi Medical University, Zhuhai 519199, China
11. Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
12. Department of Radiology, Wuhan Jinyintan Hospital, Wuhan 430048, China
13. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
14. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
15. Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 90014, Finland
16. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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Abstract

The coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (≥245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528–29.523; P <0.001) and coagulation-related biomarker D-dimer (≥0.5 μg/mL, HR= 4.321, 95% CI= 1.443–12.939; P = 0.009) and decreased albumin (<35 g/L, HR= 0.131, 95% CI= 0.048–0.361; P <0.001) and albumin/globulin ratio (<1.5, HR= 0.123, 95% CI= 0.017–0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.
Keywords COVID-19      chronic hepatitis B      liver injury      coagulation dysfunction     
Corresponding Author(s): Zhihua Wang,Jianbo Tian,Xiao-ping Chen   
About author:

Tongcan Cui and Yizhe Hou contributed equally to this work.
Just Accepted Date: 12 July 2021   Online First Date: 13 August 2021    Issue Date: 28 March 2022
 Cite this article:   
Jing Wang,Zequn Lu,Meng Jin, et al. Clinical characteristics and risk factors of COVID-19 patients with chronic hepatitis B: a multi-center retrospective cohort study[J]. Front. Med., 2022, 16(1): 111-125.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-021-0854-5
https://academic.hep.com.cn/fmd/EN/Y2022/V16/I1/111
Fig.1  Flowchart of this study. This multi-center, retrospective, and observational study was conducted at three hospitals designated for COVID-19 treatment. From January 13 to April 15, 2020, 7013 laboratory-confirmed COVID-19 patients were admitted at these hospitals. Among them, all CHB patients (N = 109) were ultimately enrolled, and 327 non-CHB patients that were statistically matched by propensity score at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities were recruited. To explore the potential risk factors associated with COVID-19 severity in CHB patients, we classified these patients into non-severe (n = 79) and severe groups (n = 30) at admission according to the guidance of the WHO for COVID-19 and the Seventh Revised Trial Version of the COVID-19 Diagnosis and Treatment Guidance (2020) of China.
Variables Total CHB Non-CHB P value
N = 436 N = 109 N = 327
Characteristics N = 436 N = 109 N = 327
Age, year, M (IQR) 57.00 (43.00–66.00) N = 109 55.00 (44.00–64.50) N = 327 57.00 (43.00–66.00) 0.669
Sex, n (%) 0.144
Male 258 (59.17) 71 (65.14) 187 (57.19)
Female 178 (40.83) 38 (34.86) 140 (42.81)
Comorbidities, n (%) N = 436 N = 109 N = 327
Hypertension 89 (20.41) 19 (17.43) 70 (21.41) 0.373
Diabetes 56 (12.84) 13 (11.93) 43 (13.15) 0.741
Coronary heart disease 30 (6.88) 7 (6.42) 23 (7.03) 0.827
Cerebral infarction 10 (2.29) 4 (3.67) 6 (1.83) 0.276a
Pulmonary tuberculosis 6 (1.38) 1 (0.92) 5 (1.53) 1.000a
Laboratory examinations
Blood routine, M (IQR)
Leukocytes, # (N = 434), × 109/L 5.46 (4.28–7.22) N = 107 6.15 (4.75–8.63) N = 327 5.24 (4.23–6.67) <0.001*
Erythrocytes, # (N = 434), × 1012/L 4.10 (3.71–4.50) N = 107 4.10 (3.62–4.55) N = 327 4.10 (3.71–4.48) 0.768
Monocytes, # (N = 429), × 109/L 0.47 (0.36–0.62) N = 102 0.48 (0.35–0.70) N = 327 0.47 (0.36–0.62) 0.423
Neutrophils, # (N = 434), × 109/L 3.40 (2.41–4.81) N = 107 4.26 (2.92–7.98) N = 327 3.25 (2.31–4.24) <0.001*
Eosinophils, # (N = 429), × 109/L 0.06 (0.02–0.13) N = 102 0.08 (0.02–0.21) N = 327 0.06 (0.01–0.11) 0.003*
Basophils, # (N = 429), × 109/L 0.01 (0.01–0.03) N = 102 0.02 (0.01–0.03) N = 327 0.01 (0.01–0.03) 0.087
Immune cell subsets, M (IQR)
Lymphocytes, # (N = 436), × 109/L 1.35 (0.97–1.81) N = 109 1.24 (0.80–1.56) N = 327 1.42 (1.00–1.84) <0.001*
CD3+CD19- T cells, # (N = 112), /μL 846.67 (617.07–1279.75) N = 35 552.80 (309.48–718.07) N = 77 1112.00 (781.50–1352.00) <0.001*
CD4+ T cells, # (N = 112), /μL 483.00 (350.03–806.50) N = 35 481.00 (236.00–644.87) N = 77 564.00 (353.97–946.00) 0.001*
CD8+ T cells, # (N = 112), /μL 352.50 (231.75–471.25) N = 35 345.00 (135.29–492.90) N = 77 353.00 (258.00–456.00) 0.366
CD3-CD19+ B cells, # (N = 97), /μL 181.00 (124.00–284.50) N = 20 129.50 (83.75–173.25) N = 77 207.00 (127.00–301.00) 0.001*
CD3-CD16+CD56+ NK cells, # (N = 97), /μL 174.00 (115.00–274.00) N = 20 150.50 (90.25–221.75) N = 77 181.00 (122.00–276.00) 0.256
T cells+ B cells+ NK cells, # (N = 97), /μL 1386.00 (936.50–1902.00) N = 20 792.04 (652.17–1103.02) N = 77 1580.00 (1161.50–1958.00) <0.001*
Inflammatory cytokines and biomarkers, M (IQR)
IL-6 (N = 352), pg/mL 3.59 (1.50–11.36) N = 69 9.92 (2.83–25.60) N = 283 3.08 (1.50–7.93) <0.001*
IL-10 (N = 337), pg/mL 5.20 (5.00–7.50) N = 58 5.00 (5.00–6.88) N = 279 5.30 (5.00–7.50) 0.373
IL-8 (N = 337), pg/mL 12.40 (6.50–24.10) N = 58 12.80 (7.15–25.68) N = 279 12.20 (6.40–23.90) 0.292
TNF-α (N = 342), pg/mL 7.30 (5.30–9.33) N = 58 9.15 (7.30–13.08) N = 284 7.00 (5.03–8.98) <0.001*
IL-1β (N = 337), pg/mL 5.00 (5.00–5.00) N = 58 5.00 (5.00–5.53) N = 279 5.00 (5.00–5.00) 0.075
IL-2R (N = 334), U/mL 497.00 (351.00–673.25) N = 58 509.00 (334.50–776.50) N = 276 495.50 (354.25–657.50) 0.401
Ferritin (N = 225), μg/L 368.90 (181.00–609.70) N = 44 470.05 (173.05–1162.50) N = 181 349.80 (183.10–582.50) 0.051
hs-CRP (N = 416), mg/L 4.50 (1.10–29.88) N = 94 19.25 (2.18–62.73) N = 322 3.70 (1.00–15.10) <0.001*
Organ damage indexes, M (IQR)
ALT (N = 435), U/L 19.00 (14.00–30.00) N = 108 31.00 (19.00–72.25) N = 327 18.00 (13.00–25.00) <0.001*
AST (N = 435), U/L 22.00 (18.00–33.00) N = 108 35.50 (21.25–64.25) N = 327 21.00 (17.00–28.00) <0.001*
TBIL (N = 435), μmol/L 8.70 (6.50–12.10) N = 108 10.25 (7.65–15.63) N = 327 8.20 (6.30–11.30) <0.001*
DBIL (N = 431), μmol/L 3.40 (2.60–4.40) N = 104 3.60 (2.90–5.93) N = 327 3.30 (2.60–4.30) 0.003*
ALB (N = 433), g/L 38.50 (34.95–41.75) N = 106 33.95 (29.28–38.55) N = 327 39.40 (36.70–42.20) <0.001*
GLO (N = 433), g/L 29.10 (25.70–31.60) N = 106 27.55 (24.68–30.33) N = 327 29.40 (26.10–31.90) 0.002*
TP (N = 433), g/L 67.80 (63.50–71.70) N = 106 61.55 (55.88–65.63) N = 327 69.30 (65.90–72.70) <0.001*
ALB/GLO (N = 433) 1.33 (1.15–1.57) N = 106 1.23 (1.03–1.50) N = 327 1.35 (1.19–1.57) <0.001*
LDH (N = 400), U/L 217.00 (180.00–265.50) N = 105 238.00 (175.00–319.00) N = 295 211.00 (180.00–251.00) 0.019*
ALP (N = 400), U/L 64.00 (48.00–87.00) N = 104 68.00 (53.25–88.50) N = 296 62.50 (46.00–84.75) 0.049*
CK-MB (N = 303), U/L 0.70 (0.40–1.20) N = 72 1.10 (0.58–9.15) N = 231 0.70 (0.40–1.00) <0.001*
PT (N = 432), s 13.60 (13.10–14.20) N = 105 14.40 (13.55–16.50) N = 327 13.50 (13.00–14.00) <0.001*
APTT (N = 428), s 37.90 (35.60–40.30) N = 101 38.10 (34.70–41.40) N = 327 37.90 (35.70–40.00) 0.512
D-dimer (N = 431), μg/mL 0.42 (0.24–0.90) N = 104 0.95 (0.32–2.64) N = 327 0.36 (0.23–0.62) <0.001*
Complication, n (%) N = 436 N = 109 N = 327 0.026*,a
DIC 8 (1.83) 5 (4.59) 3 (0.92)
Non-DIC 428 (98.17) 104 (95.41) 324 (99.08)
Severity, n (%) N = 436 N = 109 N = 327 <0.001*
Severe 72 (16.51) 30 (27.52) 42 (12.84)
Non-severe 364 (83.49) 79 (72.48) 285 (87.16)
Outcomes, n (%) N = 436 N = 109 N = 327 <0.001*
Survivor 415 (95.18) 96 (88.07) 319 (97.55)
Non-survivor 21 (4.82) 13 (11.93) 8 (2.45)
Tab.1  Demographic, clinical, radiographic, and laboratory findings of COVID-19 patients with and without CHB
Variables Total Severe Non-severe P value
N = 109 N = 30 N = 79
Characteristics N = 109 N = 30 N = 79
Age, year, M (IQR) 55.00 (44.00–64.50) N = 30 58.50 (49.25–62.75) N = 79 54.00 (42.00–65.00) 0.461
Sex, n (%) 0.269
Male 71 (65.14) 22 (73.33) 49 (62.03)
Female 38 (34.86) 8 (26.67) 30 (37.97)
Comorbidities, n (%) N = 109 N = 30 N = 79
Hypertension 19 (17.43) 5 (16.67) 14 (17.72) 0.897
Diabetes 13 (11.93) 7 (23.33) 6 (7.59) 0.042*, a
Coronary heart disease 7 (6.42) 3 (10.00) 4 (5.06) 0.391a
Cerebral infarction 4 (3.67) 1 (3.33) 3 (3.80) 1.000a
Pulmonary tuberculosis 1 (0.92) 1 (3.33) 0 (0.00) 0.275a
Laboratory examinations
Blood routine, M (IQR)
Leukocytes, # (N = 107), × 109/L 6.15 (4.75–8.63) N = 28 7.48 (5.09–8.97) N = 79 6.09 (4.72–8.46) 0.436
Erythrocytes, # (N = 107), × 1012/L 4.10 (3.62–4.55) N = 28 4.02 (2.74–4.31) N = 79 4.15 (3.80–4.55) 0.085
Monocytes, # (N = 102), × 109/L 0.48 (0.35–0.70) N = 25 0.58 (0.40–0.71) N = 77 0.46 (0.35–0.63) 0.581
Neutrophils, # (N = 107), × 109/L 4.26 (2.92–7.98) N = 28 6.18 (4.08–11.37) N = 79 4.01 (2.66–6.67) 0.001*
Eosinophils, # (N = 102), × 109/L 0.08 (0.02–0.21) N = 25 0.07 (0.00–0.24) N = 77 0.09 (0.03–0.18) 0.183
Basophils, # (N = 102), × 109/L 0.02 (0.01–0.03) N = 25 0.02 (0.01–0.04) N = 77 0.02 (0.01–0.03) 0.235
Immune cell subsets, M (IQR)
Lymphocytes, # (N = 109), × 109/L 1.24 (0.80–1.56) N = 30 1.02 (0.55–1.33) N = 79 1.28 (0.90–1.65) 0.006*
CD3+CD19- T cells, # (N = 35), /μL 552.80 (309.48–718.07) N = 10 340.25 (165.13–467.28) N = 25 582.45 (361.59–799.46) 0.014*
CD4+ T cells, # (N = 35), /μL 481.00 (236.00–644.87) N = 10 271.11 (124.73–411.50) N = 25 508.00 (291.38–721.17) 0.024*
CD8+ T cells, # (N = 35), /μL 345.00 (135.29–492.90) N = 10 295.08 (130.25–564.75) N = 25 345.00 (175.08–454.00) 0.927
CD3-CD19+ B cells, # (N = 20), /μL 129.50 (83.75–173.25) N = 8 91.50 (60.00–124.50) N = 12 161.50 (131.00–177.25) 0.012*
CD3-CD16+CD56+ NK cells, # (N = 20), /μL 150.50 (90.25–221.75) N = 8 142.00 (73.75–234.75) N = 12 158.00 (129.50–219.50) 0.440
T cells+ B cells+ NK cells, # (N = 20), /μL 792.04 (652.17–1103.02) N = 8 677.08 (358.04–797.06) N = 12 1000.33 (773.49–1145.04) 0.021*
Inflammatory cytokines and biomarkers, M (IQR)
IL-6 (N = 69), pg/mL 9.92 (2.83–25.60) N = 21 32.00 (10.92–119.47) N = 48 6.69 (2.44–14.92) <0.001*
IL-10 (N = 58), pg/mL 5.00 (5.00–6.58) N = 15 5.00 (5.00–10.00) N = 43 5.00 (5.00–6.25) 0.776
IL-8 (N = 58), pg/mL 12.80 (7.15–25.68) N = 15 13.10 (8.10–45.00) N = 43 12.40 (6.70–21.80) 0.248
TNF-α (N = 58), pg/mL 9.15 (7.30–13.08) N = 15 13.00 (9.40–17.90) N = 43 8.70 (6.40–11.30) 0.001*
IL-1β (N = 58), pg/mL 5.00 (5.00–5.53) N = 15 5.00 (5.00–5.00) N = 43 5.00 (5.00–6.30) 0.074
IL-2R (N = 58), U/mL 509.00 (334.50–776.50) N = 15 696.00 (404.50–1042.50) N = 43 502.00 (315.50–697.50) 0.153
Ferritin (N = 44), μg/L 470.05 (173.05–1162.50) N = 13 511.78 (235.10–1787.00) N = 31 417.60 (156.00–949.25) 0.286
hs-CRP (N = 94), mg/L 19.25 (2.18–62.73) N = 25 30.90 (14.25–93.85) N = 69 13.34 (1.40–47.43) 0.015*
Organ damage indexes, M (IQR)
ALT (N = 108), U/L 31.00 (19.00–72.25) N = 30 71.50 (25.50–177.25) N = 78 27.50 (17.00–52.25) 0.001*
AST (N = 108), U/L 35.50 (21.25–64.25) N = 30 52.50 (30.50–121.00) N = 78 27.50 (20.00–47.25) 0.003*
TBIL (N = 108), μmol/L 10.25 (7.65–15.63) N = 30 18.50 (10.80–33.60) N = 78 9.10 (6.60–12.05) <0.001*
DBIL (N = 104), μmol/L 3.60 (2.90–5.93) N = 26 5.65 (3.23–13.63) N = 78 3.49 (2.70–4.50) 0.008*
ALB (N = 106), g/L 33.95 (29.28–38.55) N = 28 28.20 (22.95–33.33) N = 78 35.30 (30.88–39.63) <0.001*
GLO (N = 106), g/L 27.55 (24.68–30.33) N = 28 25.70 (22.45–29.28) N = 78 27.85 (25.45–30.68) 0.013*
TP (N = 106), g/L 61.55 (55.88–65.63) N = 28 58.00 (50.40–61.35) N = 78 63.20 (58.20–66.60) <0.001*
ALB/GLO (N = 106) 1.23 (1.03–1.50) N = 28 1.12 (0.90–1.23) N = 78 1.30 (1.08–1.60) 0.001*
LDH (N = 105), U/L 238.00 (175.00–319.00) N = 28 282.00 (186.75–427.50) N = 77 224.00 (175.00–286.00) 0.025*
ALP (N = 104), U/L 68.00 (53.25–88.50) N = 26 76.50 (65.75–116.75) N = 78 64.00 (49.75–84.00) 0.012*
CK-MB (N = 72), U/L 1.10 (0.58–9.15) N = 18 1.50 (0.50–11.78) N = 54 0.95 (0.60–7.30) 0.658
PT (N = 105), s 14.40 (13.55–16.50) N = 28 16.65 (15.65–17.95) N = 77 14.10 (13.50–14.80) <0.001*
APTT (N = 101), s 38.10 (34.70–41.40) N = 26 41.15 (35.20–59.08) N = 75 37.30 (34.75–40.15) 0.017*
D-dimer (N = 104), μg/mL 0.95 (0.32–2.64) N = 28 2.02 (1.02–11.46) N = 76 0.60 (0.22–2.13) <0.001*
Complication, n (%) N = 109 N = 30 N = 79 0.020*, a
DIC 5 (4.59) 4 (13.33) 1 (1.27)
Non-DIC 104 (95.41) 26 (86.67) 78 (98.73)
Hepatitis B virus serological markers, n (%) N = 109 N = 30 N = 79 0.020*,a
HBsAg+ 102 (93.58) 28 (93.33) 74 (93.67) 1.000 a
HBsAb+ 8 (7.34) 1 (3.33) 7 (8.86) 0.441 a
HBeAg+ 11 (10.09) 11 (36.67) 0 <0.001*
HBeAb+ 92 (84.40) 18 (60.00) 74 (93.67) <0.001*
HBcAb+ 106 (97.25) 29 (96.67) 77 (97.47) 0.819
HBV DNA, # (N = 84), × 105/L 2.35 (0.73–5.68) N = 23 2.70 (0.94–4.40) N = 61 1.90 (0.69–6.40) 0.964
Anti-hepatitis therapies, n (%) N = 109 N = 30 N = 79
Past anti-HBV therapyb 74 (67.89) 22 (73.33) 52 (65.82) 0.453
Liver protective therapyc 86 (78.90) 27 (90.00) 59 (74.68) 0.080
Outcomes, n (%) N = 109 N = 30 N = 79 0.042*,a
Survivor 96 (88.07) 23 (76.67) 73 (92.41)
Non-survivor 13 (11.93) 7 (23.33) 6 (7.59)
Tab.2  Demographic, clinical, radiographic, and laboratory findings of severe and non-severe COVID-19 patients with CHB
Variables All patients
Total CHB Non-CHB P value
N = 436 N = 109 N = 327
Treatmentsb, n (%)
?Antiviral therapy 194 (44.50) 49 (44.95) 145 (44.34) 0.911
?Antibiotics 287 (65.83) 74 (67.89) 213 (65.14) 0.600
?Intravenous immunoglobulin therapy 129 (29.59) 51 (46.79) 78 (23.85) <0.001*
Glucocorticoid therapy 128 (29.36) 42 (38.53) 86 (26.30) 0.015*
High-flow oxygen therapy 19 (4.36) 6 (5.50) 13 (3.98) 0.587
Mechanical ventilation 51 (11.70) 25 (22.49) 26 (7.95) <0.001*
?Non-invasive 26 (5.96) 7 (6.42) 19 (5.81) 0.815
?Invasive 11 (2.52) 4 (3.67) 7 (2.14) 0.479a
?Transfusion 22 (5.05) 7 (6.42) 15 (4.59) 0.448
Variables CHB patients
Total Severe Non-severe P value
N = 109 N = 30 N = 79
Treatmentsb, n (%)
?Antiviral therapy 49 (44.95) 16 (53.33) 33 (41.77) 0.278
?Antibiotics 74 (67.89) 22 (73.33) 52 (65.82) 0.453
?Intravenous immunoglobulin therapy 51 (46.79) 20 (66.67) 31 (39.24) 0.010*, a
Glucocorticoid therapy 42 (38.53) 14 (46.67) 28 (35.44) 0.282
High-flow oxygen therapy 6 (5.50) 1 (3.33) 5 (6.33) 1.000a
Mechanical ventilation 25 (22.94) 9 (30.00) 16 (20.25) 0.280
?Non-invasive 7 (6.42) 6 (20.00) 1 (1.27) 0.002*, a
?Invasive 4 (3.67) 3 (10.00) 1 (1.27) 0.063a
?Transfusion 7 (6.42) 2 (6.67) 5 (6.33) 1.000a
Tab.3  Clinical treatments and complications of COVID-19 patients
Variables Univariable logistic regression Multivariable logistic regression
OR (95% CI) P value OR (95% CI) P valuea
Laboratory examinations
?Blood routine
??Neutrophils, # (N = 107), × 109/L 1.243 (1.095–1.412) 0.001* 1.236 (1.078–1.418) 0.002*
?Immune cell subsets
??Lymphocytes, # (N = 109), × 109/L 0.274 (0.110–0.683) 0.005* 0.274 (0.100–0.749) 0.012*
??CD3+CD19− T cells, # (N = 15), /μL 0.995 (0.991–0.999) 0.022* 0.995 (0.990–1.000) 0.031*
??CD4+ T cells, # (N = 35), /μL 0.996 (0.992–1.000) 0.029* 0.995 (0.991–1.000) 0.038*
?Inflammatory cytokines and biomarkers
??IL-6 (N = 69), pg/mL 1.032 (1.005–1.060) 0.021* 1.032 (1.007–1.058) 0.013*
??TNF-α (N = 58), pg/mL 1.211 (1.046–1.402) 0.010* 1.184 (1.007–1.393) 0.040*
??hs-CRP (N = 94), mg/L 1.013 (1.003–1.023) 0.013* 1.014 (1.002–1.025) 0.018*
?Organ damage indexes
??ALT (N = 108), U/L 1.011 (1.003–1.019) 0.005* 1.012 (1.004–1.020) 0.003*
??AST (N = 108), U/L 1.006 (1.000–1.012) 0.040* 1.007 (1.001–1.013) 0.027*
??ALP (N = 104), U/L 1.008 (1.000–1.017) 0.044* 1.009 (1.001–1.017) 0.030*
??TBIL (N = 108), μmol/L 1.056 (1.022–1.092) 0.001* 1.054 (1.018–1.091) 0.003*
??ALB (N = 106), g/L 0.807 (0.732–0.890) <0.001* 0.803 (0.723–0.891) <0.001*
??ALB/GLO (N = 106) 0.073 (0.014–0.386) 0.002* 0.062 (0.010–0.385) 0.003*
??LDH (N = 105), U/L 1.003 (1.000–1.006) 0.023* 1.004 (1.001–1.007) 0.021*
??Amylase (N = 44), U/L 0.983 (0.964–1.003) 0.089 0.968 (0.937–1.000) 0.048*
??hs-cTnI (N = 79), pg/mL 1.001 (1.000–1.001) 0.029* 1.001 (1.000–1.001) 0.040*
??APTT (N = 101), s 1.098 (1.034–1.165) 0.002* 1.115 (1.042–1.192) 0.002*
??D-dimer (N = 104), μg/mL 1.097 (1.021–1.178) 0.011* 1.100 (1.022–1.185) 0.012*
Tab.4  Factors associated with the illness severity of COVID-19 patients with CHB
Fig.2  Survival of COVID-19 patients during hospitalization. (A) Survival curve of COVID-19 patients with and without CHB. (B–I) Survival curves of COVID-19 patients with different levels of liver test parameters, such as ALT (B), AST (C), ALP (D), TBIL (E), and LDH (F); D-dimer coagulation index (G); ALB (H); and ALB/GLO (I). The survival curves were compared and analyzed, and the hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed by the Cox proportional hazards regression models. P<0.05 was considered statistically significant.
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