Similar baseline conditions except glucose metabolic parametersbetween four subgroups
95 patients with COVID-19 was retrospectively recruited, among them, 76 patients without DM were includedin non-DM group, including 57 non-severe cases and 19 severe cases;19 patients with DM were included in DM group,including 8 non-severe cases and 11 severe cases(Of them 8 cases newly diagnosed diabetes,including 3 non-severe cases and 5 severe cases).The prevalence of DM in COVID-19 was 20%(19/95).The severe rate of patients with DM was higher than that of patients without DM,the difference wassignificant(61.11%vs.25.55%,х2=2.940,P=0.003) .
Patients in non-severenon-DM subgroup were significantly younger than those in the other three subgroups.Patients of other threesubgroups had similar age(Table 1). No significant difference was observed in terms of gender betweenfour subgroups(Table 1). FPG levels and HbA1c levelsin DM group were obviously higher than that in non-DM group(Table 1). But there was no significant difference of glucose metabolic parameters between each intra-group(Table 1).\
Table 1. Comparison of baseline conditions and glucose metabolic parameters between four subgroups(n=95)
variable
|
non-DM group(n=76)
|
DM group(n=19)
|
х2或F值
|
P值
|
non-severe subgroup(n=57)
|
severe subgroup(n=19)
|
non-severe subgroup(n=8)
|
severe subgroup(n=11)
|
age(year)
|
42.67±14.71
|
58.00±19.24***
|
61.57±12.01***
|
59.36±12.31***
|
8.914
|
0.000
|
male(case,%)
|
25(43.86)
|
11(57.89)
|
3(37.50)
|
7(63.64)
|
2.532
|
0.469
|
FPG(mmol/L)
|
5.30±0.75
|
5.40±0.75
|
8.80±3.10****
|
8.75±2.50****
|
31.97
|
0.000
|
HbA1c(%)
|
5.70±0.80
|
5.75±0.80
|
9.10±3.60****
|
9.11±3.50****
|
10.05
|
0.000
|
Abbreviations:FPG,fasting plasma glucose;HbA1c,glycated hemoglobin A1c;DM,diabetesmellitus;non-DM, without diabetes mellitus.Compared with the non-severe non-DM subgroup,***P<0.001,****P<0.0001. Comparison of age between the latter three subgroups,P>0.05.
Overall decreased lymphocytes subsets in COVID-19 severe cases with DM
In COVID-19 severe cases with DMlymphocyte count level, lymphocytepercentage value ,CD3+ count level,CD3+CD4+ count level,CD3+CD8+ count level and B(CD19+)count levelwere the lowest, simultaneously inflammatory factor IL-6 and infection-related factors included CRP and SAA were the highest compared with that in the other three subgroups,especially non-severe non-DM and non-severe DM subgroups, the difference was significant(Table 2).
Table 2. Comparison of lymphocytes subsets,infection-related indicators and inflammatory factors at baseline between four subgroups(n=95)
|
varable
|
non-DM group(n=76)
|
DM group(n=19)
|
х2或F值
|
P值
|
non-severe subgroup(n=57)
|
severe subgroup(n=19)
|
non-severe subgroup(n=8)
|
severe subgroup(n=11)
|
lymphocyte
|
LY
|
1128.60±575.11
|
827.58±446.06*
|
1097.86±290.28
|
538.91±324.18**##
|
4.960
|
0.003
|
LY%
|
13.26±6.30
|
9.34±5.93*
|
11.44±5.86
|
6.58±3.47**#
|
5.006
|
0.003
|
lymphocyte subsets
|
CD3+(cells/ul)
|
841.32±472.61
|
538.00±314.10*
|
800.57±190.17
|
395.36±285.31**##
|
5.232
|
0.002
|
D3+%
|
73.32±8.89
|
64.05±8.83
|
73.47±9.92
|
72.29±12.46
|
4.787
|
0.004
|
▲B(CD19+)
|
104.99±1.92
|
78.01±1.87
|
97.74±1.58
|
36.77±3.63*#
|
4.466
|
0.007
|
▲B(CD19+)%
|
10.47±1.64
|
12.03±1.71
|
11.35±1.13
|
7.62±2.86
|
1.043
|
0.380
|
▲NK(CD56+)
|
109.37±1.99
|
105.48±1.99
|
152.26±1.62
|
51.92±2.00
|
3.243
|
0.028
|
▲NK(CD56+)%
|
10.87±1.97
|
16.21±1.43
|
17.14±1.86
|
11.08±1.60
|
1.933
|
0.134
|
T cell subsets
|
CD3+CD4+
|
488.28±286.14
|
280.21±157.20**
|
511.29±148.84
|
233.27±181.96**##
|
5.890
|
0.001
|
CD3+CD4+%
|
42.55±8.95
|
33.71±9.49****
|
46.67±6.93
|
41.10±12.36
|
5.184
|
0.002
|
CD3+CD8+
|
289.40±174.88
|
223.63±178.27
|
237.57±85.02
|
141.36±105.35**
|
2.833
|
0.043
|
CD3+CD8+%
|
25.69±6.50
|
26.00±10.57
|
21.53±7.46
|
27.77±10.94
|
0.866
|
0.462
|
CD4/CD8
|
1.82±0.80
|
1.60±0.86
|
2.49±1.24
|
1.83±1.18
|
1.696
|
0.173
|
inflammatory factor
|
▲CRP
|
5.93±3.36
|
17.11±3.73**
|
12.16±5.36
|
26.15±2.51****
|
6.669
|
0.000
|
▲SAA
|
21.01±3.46
|
80.58±3.95****
|
46.26±4.96
|
136.11±3.32****
|
9.752
|
0.000
|
▲IL-6
|
2.92±2.35
|
5.41±2.01
|
4.55±3.24
|
8.91±2.71**
|
3.046
|
0.044
|
Abbreviations: DM,diabetesmellitus; LY, lymphocyte.Compared with the non- severe non-DM subgroup,*P<0.05, **P<0.01,****P<0.0001. Compared with the severe non-DM subgroup,﹟P<0.05,﹟﹟P<0.01.
In COVID-19 severe cases without DM, lymphocyte count level, lymphocytepercentage value ,CD3+ count level, CD3+CD4+ count level, CD3+CD4+ percentage value were lower, simultaneouslyinfection-related factors such as CRP and SAA were higher than that in non-sever patients without DM, there were obviously statistical difference(Table 2).
More severe conditions, longer virus negative conversion time and worse prognosis in COVID-19 severe cases with DM
In COVID-19 patients with DMthe severe rate was higher and the prognosis was worse,Moreover in COVID-19 patients with DMespeciallysevere cases, the virus negative conversion time and the inhospital time were longerthan that in thosewithout DM, the difference was significant(Table 3).
Table 3. Comparison of the disease severity, the virus negative conversion time and the prognosis between four subgroups(n=95)
varable
|
non-DM group(n=76)
|
DM group(n=19)
|
х2或F值
|
P值
|
non-severe subgroup(n=57)
|
severe subgroup(n=19)
|
non-severe subgroup(n=8)
|
severe subgroup(n=11)
|
virus negative conversion time
|
18.02±8.66
|
19.26±6.84
|
24.86±11.50*
|
26.36±8.44***﹟﹟
|
4.490
|
0.006
|
inhospital time
|
13.14±6.92
|
17.79±9.91*
|
16.43±6.68*
|
24.09±10.79****﹟﹟﹟﹟
|
12.843
|
0.000
|
severe(case,%)
|
19(25.00)
|
11(61.11)
|
-2.940
|
0.003
|
prognosis
|
|
|
-3.394
|
0.001
|
cured(case,%)
|
53(71.05)
|
5(26.32)
|
unhealed
|
21(26.32)
|
13(68.42)
|
death
|
2(2.63)
|
1(5.26)
|
Abbreviations:FPG,fasting plasma glucose;HbA1c,glycated hemoglobin A1c;DM,diabetesmellitus;non-DM,without diabetes mellitus.Compared with the non-severe non-DM subgroup,*P<0.05, ***P<0.001,*** *P<0.0001. Compared with the severe non-DM subgroup,﹟﹟P<0.001,﹟﹟﹟﹟P<0.0001.
Partial decreased lymphocytes subsets as influencing factors for disease severity, coronavirus negativeconversion and prognosis in COVID-19 patients with DM
Pearson correlation analysisshowed that DM and age were positively,while lymphocytecount level,lymphocytepercentage value,CD3+ count level, CD3+CD4+ count level, CD3+CD8+ count level, CD3+ percentage value, CD3+CD4+ percentage value, B(CD19+) count level were negatively related to the disease severity(Table 4). By partial correlation analysis when controlling age,DM were still positively, lymphocytepercentage value, CD3+CD4+ count level and B(CD19+) count level were still negatively related to that. When controlling DM, age were still positively, lymphocytecount level, lymphocytepercentage value,CD3+ count level and CD3+CD4+ count level were still negatively related to that.When controlling both DM and age,lymphocytepercentage value and CD3+CD4+ count level were still negatively related to that(Table 5). The important factors influencingthe disease severity by multiple stepwise regression analysis was DM, age, lymphocytepercentage value and CD3+CD4+ percentage value(Table 6).
Table 4. Pearson correlation analysis of the disease severity,virus negative conversion time,prognosis,lymphocyte subsets, age and DM(n=95)
variable
|
disease severity(1= common,2= severe,3=critically illness)
|
virus negative conversion time(days)
|
prognosis(1=cure,2=unheal,3=death)
|
r
|
p
|
r
|
p
|
r
|
p
|
DM(1=without,2=with)
|
0.367
|
0.000
|
0.331
|
0.001
|
0.412
|
0.000
|
age(year)
|
0.383
|
0.000
|
0.304
|
0.003
|
0.41
|
0.000
|
LY(cells/ul)
|
-0.379
|
0.000
|
|
|
-0.299
|
0.004
|
LY%(%)
|
-0.394
|
0.000
|
|
|
-0.355
|
0.001
|
CD3+(cells/ul)
|
-0.387
|
0.000
|
|
|
-0.215
|
0.000
|
CD3+CD4+(cells/ul)
|
-0.404
|
0.000
|
|
|
-0.28
|
0.030
|
CD3+CD8+(cells/ul)
|
-0.277
|
0.007
|
|
|
-0.285
|
0.006
|
CD+3%(%)
|
-0.262
|
0.011
|
|
|
-0.262
|
0.011
|
CD3+CD4+%
|
-0.274
|
0.007
|
|
|
|
|
CD19+(cells/ul)
|
-0.302
|
0.017
|
0.293
|
0.021
|
|
|
disease severity(1= common,2= severe,3=critically illness)
|
|
|
|
|
0.438
|
0.000
|
virus negative conversion time(days)
|
|
|
|
|
0.457
|
0.000
|
Abbreviations: DM,diabetesmellitus. LY, lymphocytes.
Table 5. Partial correlation analysis of the disease severityvirus negative conversion time,prognosis,lymphocyte subsets, age and DM(n=95)
control variable
|
variable
|
disease severity(1= common,2= severe,3=critically illness)
|
virus negative conversion time(days)
|
prognosis(1=cure,2=unheal,3=death)
|
r
|
p
|
r
|
p
|
r
|
p
|
age(year)
|
diabetes mellitus(1=without,2=with)
|
0.313
|
0.015
|
0.378
|
0.003
|
0.301
|
0.02315
|
CD3+CD4+(cells/ul)
|
-0.260
|
0.045
|
|
|
|
|
lymphocyte%(%)
|
-0.351
|
0.006
|
|
|
|
|
CD19+(cells/ul)
|
-0.255
|
0.049
|
0.299
|
0.023
|
|
|
|
disease severity(1= common,2= severe,3=critically illness)
|
|
|
|
|
0.265
|
0.046
|
|
virus negative conversion time(days)
|
|
|
|
|
0.567
|
0.000
|
diabetes mellitus(1=without,2=with)
|
age(year)
|
0.311
|
0.015
|
|
|
0.355
|
0.007
|
CD3+(cells/ul)
|
-0.302
|
0.019
|
|
|
|
|
CD3+CD4+(cells/ul)
|
-0.322
|
0.012
|
|
|
|
|
lymphocyte(cells/ul)
|
-0.299
|
0.020
|
|
|
|
|
lymphocyte%(%)
|
-0.359
|
0.005
|
|
|
|
|
|
CD19+(cells/ul)
|
|
|
0.393
|
0.002
|
|
|
|
disease severity(1= common,2= severe,3=critically illness)
|
|
|
|
|
0.256
|
0.054
|
|
virus negative conversion time(days)
|
|
|
|
|
0.526
|
0.000
|
age(year) and diabetes mellitus(1=without,2=with)
|
CD3+CD4+(cells/ul)
|
-0.272
|
0.037
|
|
|
|
|
lymphocyte%(%)
|
-0.327
|
0.011
|
|
|
|
|
|
CD19+(cells/ul)
|
|
|
0.389
|
0.003
|
|
|
|
virus negative conversion time(days)
|
|
|
|
|
0.507
|
0.000
|
Abbreviations: DM,diabetesmellitus. LY, lymphocytes.
Table 6. Multiple stepwise regression analysis of influencing factors of the disease severity,the coronavirus negative conversion time and the prognosis
independent variable
|
|
B
|
Std. Error
|
Beta
|
t
|
p
|
the disease severity
|
constant
|
1.471
|
0.384
|
-
|
3.828
|
0.000
|
DM(1=without,2=with
|
0.537
|
0.185
|
0.266
|
2.897
|
0.005
|
age
|
0.013
|
0.004
|
0.275
|
3.007
|
0.003
|
CD3+CD4+%
|
-0.023
|
0.007
|
-0.287
|
-3.236
|
0.002
|
LY%
|
-0.025
|
0.012
|
-0.200
|
-2.173
|
0.032
|
the coronavirus negative conversion time
|
constant
|
18.421
|
3.173
|
-
|
5.805
|
0.000
|
CD19+%(%)
|
0.394
|
0.184
|
0.255
|
2.134
|
0.037
|
LY%(%)
|
-0.413
|
0.171
|
-0.290
|
-2.422
|
0.019
|
the prognosis
|
constant
|
0.33
|
0.161
|
-
|
2.067
|
0.042
|
coronavirus negative conversion time
|
0.022
|
0.006
|
-0.354
|
4.005
|
0.000
|
disease severity
|
0.220
|
0.063
|
0.316
|
3.481
|
0.001
|
age
|
0.007
|
0.003
|
0.204
|
2.141
|
0.035
|
Abbreviations: DM,diabetesmellitus. LY, lymphocytes count.
By pearson correlation analysis of the viral negative conversion time positiverelevant factors were DM and age, and negative relevant factor was B(CD19+) count level(Table 4). Using partial correlation analysis when controlling age,DM was positive and B(CD19+) count level was negative relevant factors. Whether controlling DM alone or both diabetes and age, only B(CD19+) count level was negative relevant factor (Table 5).Influencing factors of the virus negative conversion time by multiple stepwise regression analysis was lymphocytepercentage value and B(CD19+) percentage value (Table 6).
Related to theprognosis positive factorswere DM, age,the disease severity and the coronavirus negative conversion time,negative factorswerelymphocytecount level, lymphocytepercentage value, CD3+ count level, CD3+CD4+ count level, CD3+CD8+ count level and CD3+ percentage value(Table 4).By partial correlation analysis,when controlling age only positive factors included DM, the disease severity and the coronavirus negative time were found,when controlling DM the positive factors included age,the disease severity and the coronavirus negative time. When controlling both DM and age,only the coronavirus negative time were positive factor(Table 5). Influencing factors of the prognosis by multiple stepwise regression analysis was age, the disease severity and the coronavirus negative conversion time(Table 6).