2.1 Basic information about patients
A total of 466 patients with uremia combined with maintenance hemodialysis (MHD) were collected, 39 patients with incomplete data were excluded, and a total of 427 patients were included for analysis. They ranged from 27 to 88 years old, with an average age of (57.1±12.7) years. Among MHD patients, the severity of disease after infection was not related to gender, including 292 males (68.4%) and 135 females (31.6%). However, age is an important factor affecting the severity of the patient's disease, and there is no significant difference in the severity of COVID-19 infection among the groups with underlying diseases and smoking history (Table 1). The results of clinical symptoms in each group showed that most patients in each group presented cough, fever, and digestive tract symptoms. There were significant differences in the clinical manifestations of cough, runny nose, myalgia, and gastrointestinal symptoms among all groups (P < 0.05) (Table 1). The main symptoms of severe and critically ill patients are fever and cough, and the common type also presents fever, accounting for a higher proportion. Most mild patients have no obvious clinical manifestations (Table 1). The symptoms of shortness of breath and fatigue are very common in dialysis patients, which can be caused by cardiac insufficiency and lung infection. Almost all patients did not have regular dialysis before hospitalization due to the epidemic and had shortness of breath and fatigue symptoms, which were difficult to identify, so they were not included in the statistics. In this study, all patients received the pharyngeal swab nucleic acid tests on admission. The more critical the diagnosis grade was, the lower the Ct values of ORF1ab and N genes of SARS-CoV-2 patients, indicating higher viral load. (P < 0.001) (Table 1).
Table 1. Comparison of the basic situation of patients with MHD combined with COVID-19 infection in different clinical subtypes [No. (%)]
|
Median (IQR) or Mean ± SD or No. (%)]
|
χ2 value
|
P value
|
Total
|
Mild
|
Common
|
Severe
|
Critical
|
(n=427)
|
160 (37.5)
|
151 (35.4)
|
96 (22.5)
|
20 (4.7)
|
Gender
|
|
|
|
|
|
|
|
Male
|
292 (68.4)
|
116 (39.7)
|
102 (34.9)
|
60 (20.5)
|
14 (4.8)
|
2.864
|
0.413
|
Female
|
135 (31.6)
|
44 (32.6)
|
49 (36.3)
|
36 (26.7)
|
6 (4.4)
|
Age group (years)
|
|
|
|
|
|
|
18~<46
|
57 (13.3)
|
25 (43.9)
|
25 (43.9)
|
7 (12.3)
|
0 (0.0)
|
19.660
|
0.021
|
46~<60
|
193 (45.2 )
|
72 (37.3)
|
73 (37.8)
|
41 (21.2)
|
7 (3.6)
|
60~<75
|
129 (30.2 )
|
41 (31.8)
|
41 (31.8)
|
37 (28.7)
|
10 (7.8)
|
≥75
|
48 (11.2)
|
22 (45.8)
|
12 (25.0)
|
11 (22.9)
|
3 (6.3)
|
Disease
|
|
|
|
|
|
|
|
Smoke
|
25 (5.9)
|
7 (4.4)
|
12 (8.0)
|
6 (6.3)
|
0 (0.0)
|
3.106
|
0.375
|
Diabetes
|
193 (45.2)
|
69 (43.1)
|
69 (45.7)
|
46 (47.9)
|
9 (45.0)
|
0.579
|
0.901
|
Hypertension
|
333 (78.0)
|
132 (82.5)
|
108 (71.5)
|
79 (82.3)
|
14 (70.0)
|
7.352
|
0.061
|
Cardiovascular event
|
114 (26.7)
|
38 (23.8)
|
40 (26.5)
|
27 (28.1)
|
9 (45.0)
|
4.237
|
0.237
|
Pulmonary disease
|
26 (6.1)
|
6 (3.8)
|
8 (5.3)
|
9 (9.4)
|
3 (15.0)
|
6.286
|
0.098
|
Circumstances of death
|
24 (5.6)
|
0 (0.0)
|
2 (1.3)
|
11 (11.5)
|
11 (55.0)
|
112.880
|
<0.001
|
symptom
|
|
|
|
|
|
|
|
Cough
|
219 (51.3)
|
61 (38.1)
|
90 (59.6)
|
55 (57.3)
|
13 (65.0)
|
18.165
|
<0.001
|
Conjunctivitis
|
54 (12.6)
|
21 (13.1)
|
16 (10.6)
|
15 (15.6)
|
2 (10.0)
|
1.506
|
0.681
|
Runny nose
|
32 (7.5)
|
6 (3.8)
|
13 (8.6)
|
7 (7.3)
|
6 (30.0)
|
21.580
|
0.001
|
Hypophoria
|
10 (2.3)
|
2 (1.3)
|
4 (2.6)
|
4 (4.2)
|
0 (0.0)
|
2.774
|
0.428
|
Myalgia
|
38 (8.9)
|
7 (4.4)
|
17 (11.3)
|
10 (10.4)
|
4 (20.0)
|
8.389
|
0.039
|
Sore throat
|
91 (21.3)
|
23 (14.4)
|
39 (25.8)
|
23 (24.0)
|
6 (30.0)
|
7.729
|
0.052
|
Hemoptysis
|
49 (11.5)
|
14 (8.8)
|
22 (14.6)
|
10 (10.4)
|
3 (15.0)
|
2.943
|
0.4
|
Fever
|
241 (56.4)
|
21 (13.1)
|
141 (93.4)
|
63 (65.6)
|
16 (80.0)
|
213.710
|
<0.001
|
Digestive symptom
|
82 (19.2)
|
16 (10.0)
|
37 (24.5)
|
24 (25.0)
|
5 (25.0)
|
13.980
|
0.003
|
Nucleic acid testing (NAT)
|
|
|
|
|
|
|
|
ORF1ab gene
|
31.6[28.7,35.2]
|
33.0[29.1,36.7]
|
31.5[28.2,34.6]
|
31.7[28.8,35.3]
|
25.8[21.9,30.6]
|
27.184
|
<0.001
|
N gene
|
30.2[27.1,33.4]
|
31.3[27.6,34.8]
|
30.1[27.3,33.1]
|
29.9[26.4,33.4]
|
24.5[21.6,28.7]
|
25.254
|
<0.001
|
2.2 The severity of the patient's disease
Among 427 patients infected with SARS-CoV-2, 160 were mild cases, accounting for 37.5% of the total number. There were 151 patients with the common type (35.4%), 96 patients with the severe type (22.5%), and 20 patients with the critical type (4.7%) (Fig. 1).
Blood routine results of all groups suggested that the increase of serum CRP level was related to the severity of the disease, and there was an upward trend from mild to critical type, especially the critical type was significantly higher than the other groups, and there was a statistical difference between the four groups. There was no significant difference in leukocyte, lymphocyte count, neutrophil, hemoglobin, and platelet among the four groups. In addition, it suggested that the serum level of procalcitonin in bacterial infection was statistically significant among all groups, especially in severe cases. It was speculated that SARS-CoV-2 infection combined with bacterial infection was an important cause of the critical disease trend. There were significant differences in plasma levels of sodium ions and bicarbonate ions among all groups, and bicarbonate ions tended to decrease with the aggravation of typing. It was speculated that since the patients in this study were all MHD patients, the viral and bacterial infection might lead to more serious acidosis, which was difficult to correct. Oxygen partial pressure decreased significantly with the severity of the disease (P < 0.001); There was no significant difference in the clotting-related indexes including D-dimer among all groups. Cardiovascular-related laboratory results, especially BNP, CKMB, troponin, and other groups, showed no statistical significance. Considering that MHD patients combined with infection had decreased cardiac function to varying degrees, although the results were all increased, there was no difference between groups, and no significant statistical difference was found in other indicators among groups (Table 2).
Table 2. Comparison of auxiliary examination results in patients with different clinical subtypes
|
Median (IQR) or Mean ± SD or No. (%)]
|
χ2 value
|
P value
|
Mild
|
Common
|
Severe
|
Critical
|
160(37.5)
|
151(35.4)
|
96(22.5)
|
20(4.7)
|
WBC
|
4.54[3.21,6.12]
|
4.63[3.55,5.82]
|
4.22[3.22,5.73]
|
5.65[3.83,6.8]
|
4.34
|
0.23
|
LYM
|
0.82[0.57,1.17]
|
0.67[0.46,1.37]
|
0.79[0.53,1.4]
|
0.91[0.41,2.42]
|
1.65
|
0.65
|
NE
|
3.03[1.65,4.22]
|
2.61[1.11,4.15]
|
2.54[1.45,3.65]
|
2.32[1.2,4.7]
|
4.44
|
0.22
|
HGB
|
102[88,116]
|
102[88,113]
|
97[85,113]
|
108[82,119]
|
2.31
|
0.51
|
PLT
|
140.5[111.5,202]
|
150[116,204]
|
149.5[100.8,189]
|
153.5[125.3,222.8]
|
3.29
|
0.35
|
CRP
|
12.17[3.93,31.25]
|
10.83[4.16,36.48]
|
15.04[6.06,61.01]
|
54[15.99,107.4]
|
12.04
|
0.01
|
PCT
|
0.22[0.16,0.64]
|
0.46[0.17,1.03]
|
0.56[0.36,1.33]
|
1.52[0.68,4.43]
|
38.21
|
<0.001
|
K
|
4.9[4.4,5.62]
|
4.99[4.4,5.6]
|
4.8[4.4,5.38]
|
5.2[4.38,6.04]
|
2.07
|
0.56
|
Na
|
137[135,140]
|
136[134,139]
|
137[134,140]
|
140[135,141]
|
8.88
|
0.03
|
Ca
|
2.07[1.89,2.2]
|
2.05[1.95,2.21]
|
2.07[1.92,2.2]
|
2.00[1.81,2.15]
|
0.55
|
0.91
|
P
|
1.92[1.35,2.61]
|
2.10[1.49,2.52]
|
2.08[1.42,2.68]
|
1.80[1.33,2.5]
|
6.82
|
0.1
|
HCO3-
|
21.80[18.55,24.26]
|
20.80[17.40,22.70]
|
21.01[19.18,24.28]
|
18.50[16.75,21.00]
|
9.25
|
0.03
|
ALT
|
13[9,19]
|
12[9,19]
|
13[8,20]
|
15[10,58]
|
2.2
|
0.53
|
AST
|
16[11,24]
|
16[11,26]
|
17[12,23]
|
20[14,66]
|
3.59
|
0.31
|
GLOB
|
27.6[24.9,30]
|
28.2[25.5,31.5]
|
28.0[24.9,31.5]
|
29.2[24.5,31.3]
|
1.73
|
0.63
|
ALB
|
37.5[35.1,40.2]
|
37.8[34.3,40.6]
|
38.0[35.8,40.1]
|
35.7[33.8,40.7]
|
1.61
|
0.66
|
BUN
|
22.6[19,30.8]
|
27[18.9,35.8]
|
30.6[20.8,37.3]
|
31.3[25.3,42.1]
|
2.71
|
0.44
|
SCR
|
881[707,1,258]
|
1,150[766,1,489]
|
1,035[647,1,342]
|
997[613,1,335]
|
10.04
|
0.02
|
UA
|
330[403,494]
|
415[500,555]
|
326[431,550]
|
428[487,592]
|
7.41
|
0.06
|
LDH
|
219[192,259]
|
229[180,375]
|
208[173,277]
|
284[216,747]
|
3.17
|
0.37
|
cTnI
|
0.06[0.04,0.14]
|
0.08[0.03,0.18]
|
0.1[0.04,0.25]
|
0.13[0.06,0.55]
|
5.49
|
0.14
|
cTnT
|
0.07[0.04,0.16]
|
0.12[0.05,0.29]
|
0.09[0.06,0.16]
|
0.11[0.03,0.25]
|
1.27
|
0.74
|
CKMB
|
2.1 [1.1 ,9.0]
|
4.7 [1.0 ,15.0]
|
9.2 [1.4 ,13.0]
|
18.5 [8.3 ,54.5]
|
7.65
|
0.05
|
CK
|
67.7 [39.3,130.5]
|
83 [53,257]
|
88.1 44.5,206.8]
|
121 [43.7,1037.5]
|
2.52
|
0.47
|
NT-BNP
|
266 [63 ,1499]
|
424 [103 2279]
|
849 [238 ,2562]
|
113 [320 ,1536]
|
2.62
|
0.45
|
Po2
|
103[88,119]
|
102[93,126]
|
78[70,84]
|
53[38,65]
|
122.4
|
<0.001
|
D-dimer
|
0.75[0.29,1.42]
|
0.85[0.56,1.36]
|
0.97[0.6,1.45]
|
1.17[0.69,2.17]
|
4.451
|
0.217
|
PT
|
11.6[10.8,12.3]
|
11.7[10.9,12.6]
|
11.5[11.0,12.3]
|
12.3[11.3,12.9]
|
6.03
|
0.11
|
APTT
|
33.0[29.6,36.4]
|
32.3[30.3,36.4]
|
35.0[31.7,39.0]
|
35.8[28.8,39.9]
|
2.15
|
0.542
|
FIB
|
3.85[3.13,4.84]
|
3.99[3.19,4.54]
|
4.17[3.5,5.04]
|
4.29[3.6,4.83]
|
3.05
|
0.38
|
Abbreviations: WBC: white blood cell; LYM: lymphocyte; NE: neutrophilic granulocyte; HGB: hemoglobin; PLT: platelet,; CRP: C-reactive protein; PCT: procalcitonin,; K: potassium; Na: sodium; Ca: calcium; P: phosphonium; HCO3-:carbonic acid hydrogen radical; PO2:oxygen partial pressure; DD: d-dimmer; PT: prothrombin time; APTT: activated partial thromboplastin time; FIB: fibrinogen; ALT: alanine transaminase; AST: aspartate aminotransferase; ALB: albumin; GLOB: globulin; BUN: blood urea nitrogen; SCR: creatinine; UA: uric acid; LDH: lactate dehydrogenase; cTnT: cardiac troponin T; cTnI: cardiac troponin I; CK: creatine kinase; CK-MB: creatine kinase isoenzymes MB; BNP: brain natriuretic peptide.
2.3 Treatment options and strategies
In this study, all hospitalized MHD patients did not receive the vaccine injection. Patients with bacterial infections were given antibiotics, and other treatments included regular hemodialysis, maintenance of dry weight, antipyretic treatment, and nutritional support.
Nutritional support treatment was provided to all patients based on their disease condition. MHD patients with normal digestive function and no masticatory dysfunction were primarily given enteral nutrition, which included an adequate energy intake (around 1800-2000kcal/day) and a high-protein diet (75-80g/day) during the infection. For MHD patients who were unable to eat on their own, intravenous nutrition was administered.
Patients with hypoalbuminemia (albumin levels below 30g/L) were given albumin supplements to improve their condition as soon as possible. Dialysis was strengthened to maintain optimal dry weight, and efforts were made to ensure that all patients received at least 10 hours of hemodialysis per week. Patients without a bleeding tendency were routinely dialyzed with low molecular weight heparin for anticoagulation. For patients with elevated D-dimer levels, appropriate anticoagulant therapy was administered on interdialytic days based on their disease condition.
2.4 Prognosis
In this study, there were 427 MHD patients with COVID-19, and 24 died, accounting for 5.6% of the total number. The median time from onset to death was 9d, the mode was 7d, the shortest was 2 days, and the longest was 29 days (Fig. 2). In addition to mild patients, there were no deaths in the other three grades, and the death of critical patients accounted for 55% of the death of this type (Table 3). And with the increase in age, the diagnosis grade tends to be more critical type. Classification of different severity. There were 24 deaths: 17 males and 7 females (The central causes of the disease were 12 cases, including 9 cases of cardiac arrest and 3 cases of the acute coronary syndrome and cardiogenic shock; 10 patients with severe pulmonary infection combined with septic shock, 2 patients with cerebral hemorrhage, and patients with cardiac and respiratory arrest were not diagnosed clearly. Due to the incomplete examination of rapid rescue, most patients only had laboratory indicators, so they were classified as cardiogenic factors).
Table 3. Mortality of different severity of disease
Diagnostic grading of COVID-19
|
n
|
Number of deaths and percentage of deaths [n(% )]
|
Number of deaths and percentage of COVID-19 diagnosis [n(% )]
|
Mild
|
160
|
0 (0.00%)
|
0 (0.00%)
|
Ordinary
|
151
|
2 (8.3%)
|
2 (1.32%)
|
Heavy
|
96
|
11 (45.8%)
|
11 (11.46%)
|
Critical
|
20
|
11 (45.8%)
|
11 (55.00%)
|
χ2 Value
|
112.88
|
P Value
|
<0.001
|
2.5 Multivariate regression analysis of diagnostic grading
Next, multivariate regression analysis was used to analyze possible risk factors for MHD patients infected with SARS-CoV2BA5.2 pedigree, and the results showed that age, ORF1ab gene value, PO2, and fever were independent risk factors for determining the severity of the disease (Table 4). According to the results, the prediction model is established by the formula as follows: multivariate Log it (P) =-α2+β1x1+....; Through statistical results, several independent influencing factors can predict the probability of different severity of patients' disease.
Model:
Log it (P Ordinary)=7.840+0.021×age-0.059×ORF1ab gene value-0.052×Po2-2.352×fever
Log it (P Heavy)=5.519+0.021×age-0.059×ORF1ab gene value-0.052×Po2-2.352×fever
Log it (P Critical)=2.682+0.021×age-0.059×ORF1ab gene value-0.052×Po2-2.352×fever
Table 4. Classification and ordered Logistic multivariate regression analysis
index
|
B
|
SM
|
wald
|
P
|
95% confidence interval
|
Lower limit
|
Upper limit
|
[Common = 1]
|
-7.840
|
2.317
|
11.449
|
0.001
|
-12.382
|
-3.299
|
[Severe = 2]
|
-5.519
|
2.302
|
5.749
|
0.016
|
-10.031
|
-1.008
|
[Critical = 3]
|
-2.682
|
2.289
|
1.372
|
0.241
|
-7.169
|
1.806
|
age
|
0.021
|
0.009
|
5.448
|
0.020
|
0.003
|
0.039
|
ORF1ab gene value
|
-0.059
|
0.024
|
5.912
|
0.015
|
-0.106
|
-0.011
|
CRP
|
0.001
|
0.002
|
0.150
|
0.699
|
-0.004
|
0.005
|
PCT
|
0.041
|
0.058
|
0.503
|
0.478
|
-0.073
|
0.155
|
Na
|
0.010
|
0.012
|
0.785
|
0.375
|
-0.013
|
0.034
|
HCO3-
|
-0.040
|
0.023
|
3.092
|
0.079
|
-0.085
|
0.005
|
Po2
|
-0.052
|
0.007
|
51.961
|
<0.000
|
-0.066
|
-0.038
|
SCR
|
-0.001
|
0.001
|
1.812
|
0.178
|
-0.003
|
0.001
|
[cough=0]
|
-0.305
|
0.229
|
1.773
|
0.183
|
-0.754
|
0.144
|
[Runny nose=0]
|
-0.572
|
0.393
|
2.116
|
0.146
|
-1.343
|
0.199
|
[myalgia=0]
|
0.132
|
0.358
|
0.137
|
0.712
|
-0.568
|
0.833
|
[fever=0]
|
-2.352
|
0.259
|
82.596
|
<0.000
|
-2.859
|
-1.845
|
[digestion=0]
|
0.044
|
0.270
|
0.026
|
0.872
|
-0.487
|
0.574
|
2.6 Follow-up of surviving MHD patients
A total of 427 MHD patients were followed up for the nucleic acid duration, excluding the 24 fatal cases (Fig. 3). The longest duration of positive nucleic acid was 47 days, while the median duration of negative nucleic acid was 11 days. All patients were followed up for two months, and no deaths occurred during this period.
Out of the 427 patients, 12 presented a second positive ORF1ab gene during the observational follow-up period. The median time from the first SARS-CoV-2 infection to the second positive result was 15 days. Notably, all 12 patients were asymptomatic.