The study population was 455 hospitalized diabetic patients with COVID-19. Table 1 shows characteristics and disease-related symptoms in the study population on admission, overall and by survivor status. Overall, the mean age (SD) of patients was 63.8 (13.5), and 190 (41.8%) were male. The most common comlaints at prsentaion were shortness of breath (56.7%), caugh (45.9%), fever (37.4%), and tiredness (23.3%). At admission, lack of consciousness and O2 saturation less than 93% were observed in 5.7% (26) and 58.0% (264) of patients, respectively. Overall, 69.5% (316) of patients reported at least one comorbidity; the common comorbidities, in order of frequency, were HTN (54.0%), CVD (43.7%) and CKD (22.2%). The use of ACEIs /ARBs and statins was reported in 42.9% (190) and 28.9% (117) of patients, respectively.
Table 1
Characteristics and disease-related symptoms in the study population on admission, overall and by survivor status
Characteristics
|
Total
N = 455
|
Non-survivors
N = 79
|
Survivors
N = 376
|
P –value
|
Age Mean (SD)
|
63.8 (13.5)
|
69.4 (12.2)
|
62.6 (13.5)
|
< 0.001
|
Age ≥ 65 years, % (N)
|
47.9% (218)
|
65.8% (52)
|
44.1% (166)
|
< 0.001
|
Gender: Male, % (N)
|
41.8% (190)
|
49.4% (39)
|
40.2% (151)
|
0.131
|
Symptoms, % (N)
|
|
|
|
|
Caught
|
45.9% (209)
|
36.7% (29)
|
47.9% (180)
|
0.070
|
Fever
|
37.4% (170)
|
39.2% (31)
|
37.0 (139)
|
0.704
|
Shortness of breath
|
56.7% (258)
|
62.0% (49)
|
55.6% (209)
|
0.294
|
Tiredness
|
23.3% (106)
|
16.5% (13)
|
24.7% (93)
|
0.114
|
Lack of consciousness, % (N)
|
5.7% (26)
|
16.5% (13)
|
3.5% (13)
|
< 0.001
|
O2 saturation <93%
% (N)
|
58.0% (264)
|
88.6% (70)
|
51.6% (194)
|
< 0.001
|
Comorbidities, % (N)
|
|
|
|
|
HTN
|
54.0% (239)
|
60.5% (46)
|
52.6% (193)
|
0.206
|
CVD
|
43.7% (199)
|
51.9% (41)
|
42.0% (158)
|
0.108
|
CKD
|
22.2% (101)
|
35.4% (28)
|
19.4% (73)
|
0.002
|
Other*
|
10.1% (46)
|
16.7% (13)
|
8.8% (33)
|
0.036
|
Number of Comorbidities, % (N)
|
|
|
|
|
0
|
30.5% (139)
|
22.8% (18)
|
32.2% (121)
|
0.008†
|
1
|
25.7% (117)
|
21.5% (17)
|
26.6% (100)
|
2
|
29.5% (134)
|
32.9% (26)
|
28.7% (108)
|
≥ 3
|
14.3% (65)
|
22.8% (18)
|
12.5% (47)
|
Drug History
|
|
|
|
|
ACEIs or ARBs
|
42.9% (190)
|
50.0% (38)
|
41.4% (152)
|
0.169
|
Statins
|
28.9% (117)
|
34.3% (24)
|
27.8% (93)
|
0.273
|
ACEIs = angiotensin-converting enzyme inhibitors. ARBs = angiotensin II receptor blockers. CKD = Chronic Kidney diseases. CVD = Cardiovascular diseases. HTN = Hypertension. IQR = Inter quartile range. ICU = Intensive care unit
*Cancer, rheumatism, immunodeficiency, or chronic diseases of respiratory, liver, and blood
†: linear-by-linear association test
|
During hospitalization, out of 455 patients, 98(21.5%) received ICU care, 65(14.3%) required invasive mechanical ventilation, and 79 (17.4%) dead. The median time from admission to discharge was 3 days (IQR: 1–6 days), and the median time to death was 4 days (2–8 days).
Compared to survivors, patients who dead (non-survivors) were significantly older (mean (SD) age: 69.4 years (12.2) vs. 62.6 years (13.5); P < 0.001), were more likely to have underlying comorbidity CKD (35.4% (28) vs. 19.4% (73); P = 0.002). In terms of numbers of comorbidities, a higher percentage of non-survivors had 3 or more comorbidities (22.8 vs. 12.5%; P = 0.008) than survivors.
Non-survivors were more likely to present with lack of consciousness (16.5% vs. 3.5%) and O2 saturation less than 93% (88.6% vs. 51.6%) than survivors. (Both p –values < 0.001)
The frequency of the common complaints, ACEIs /ARBs and statins users, also the comorbidities HTN and CVD all were similar between survivors and non-survivors. (All p –values > 0.05)
Laboratory findings on admission of the study population are presented in Table 2, overall and by survivor status. A lower lymphocyte count (median (IQR): 1.14 (0.78–1.8) vs. 2.25 (1.52–2.87); P-value < 0.001), but a higher count of WBC (9.8 (6.7–13.4) vs. 7.1 (5.4–9.2), P-value = 0.004) and neutrophil (8.34 (7.70–8.71) vs. 7.00 (6.20–7.75); P-value < 0.001) was observed in non-survivors compared to survivors. Also, Non-survivors significantly had a higher concentration of serum creatinine, CRP, and LDH, CPK, CPK-MB, but a lower concentration of Hb than survivors (all P-values < 0.05).
Table 2
Laboratory findings on admission of the study population, overall and by survivor status
Characteristics
|
Total
Median (IQR*)
|
Non-survivors
Median (IQR*)
|
Survivors
Median (IQR*)
|
P-value
|
WBC count, × 109/L
|
7.3 (5.4, 10.5)
|
9.8 (6.7–13.4)
|
7.1 (5.4–9.2)
|
0.004
|
Lymphocyte count,× 109/L
|
2.01 (1.21–2.87)
|
1.14 (0.78–1.8)
|
2.25 (1.52–2.87)
|
< 0.001
|
Neutrophil count,× 109/L
|
7.29 (6.22– 8.23)
|
8.34 (7.70–8.71)
|
7.00 (6.20–7.75)
|
< 0.001
|
AST, U/L
|
36.0 (26.0–51.0)
|
33.5 (20.25-54.0)
|
29.0 (18.0–43.0)
|
0.087
|
ALT, U/L
|
30.0 (18.0-43.5)
|
45.5 (31.0–83.0)
|
34.0 (25.0-46.5)
|
0.118
|
Creatinine, mg/dl
|
1.1 (0.9–1.5)
|
1.4 (0.9–2.2)
|
1.1 (0.9–1.4)
|
0.020
|
LDH, U/L
|
474.0 (356.7-629.4)
|
674.0 (487.0–932.0)
|
437.0 (350.0-587.0)
|
0.002
|
Hb, g/dL
|
12.65 (11.30–14.1)
|
12.1 (10.9–13.3)
|
12.8 (11.6–14.1)
|
0.008
|
Esr, mm/h
|
44.5 (23.75-75.0)
|
43.5 (29.5–84.0)
|
44.5 (22.0-74.5)
|
0.872
|
CRP, mg/l
|
25.0 (7.0–73.0)
|
53.8 (21.0–79.0)
|
25.0 (5.75-72.0)
|
0.015
|
Cpk, U/L
|
88.5 (58.4–151.0)
|
115.0 (70.0-222)
|
81.7 (58.0-150.0)
|
0.016
|
Cpk-MB, IU/L
|
22.0 (15.0–30.0)
|
27.4 (19.0-40.3)
|
20.0 (14.0–29.0)
|
0.019
|
FBS, mg/dl
|
174 (138.0-224)
|
192.0 (153.0-262.0)
|
166.0 (134.0-216.0)
|
0.061
|
*IQR = Inter quartile range
ALT = Alanine transaminases. AST = Aspartate transaminases. CRP = C-reactive protein. CPK = Creatine phosphokinase. CK-MB = creatine kinase myocardial band, Esr = Erythrocyte sedimentation rate. FBS = fasting blood sugar Hb = Hemoglobin. LDH: Lactate dehydrogenase. PT = Prothrombin time. WBC = White blood cell
|
Table 3 presents AUC and its 95% confidence interval (CI) of laboratory parameters for predicting COVID-19 death and optimal cutoff points of these parameters. Among assessed parameters, neutrophil count (AUC (95% CI): 0.76 (0.69–0.82)), lymphocyte count (0.75 (0.68–0.81)) and LDH level (0.74 (0.64–0.84)) had the highest diagnostic accuracy for the early detection of COVID-19 death, respectively. Besides, the concentrations of ALT and Esr were non-significant predictors of COVID-19 death.
The optimal cutoff point (sensitivity; specificity) of lymphocyte count, neutrophil count, and LDH level to discriminate between survivors and non-survivors was 1.51 × 109/L (72.1, 70.3), 8.0 × 109/L (67.2, 74.3), and 544 U/L (71.9, 72.8), respectively.
Table 3
AUC and Optimal Cut Points of Laboratory test for predicting COVID-19 death in Diabetic patients
Test
|
AUC (95% CI)
|
P-value
|
Optimal cutoff point
|
Sensitivity %
|
Specificity %
|
WBC count, × 109 /L
|
0.66 (0.59–0.73)
|
< 0.001
|
8.1
|
60.0
|
61.7
|
Lymphocyte count,× 109/L
|
0.75 (0.68–0.81)
|
< 0.001
|
1.51
|
72.1
|
70.3
|
Neutrophil count,× 109/L
|
0.76 (0.69–0.82)
|
< 0.001
|
8.0
|
67.2
|
74.3
|
Hb, g/dL
|
0.61 (0.54–0.68)
|
0.003
|
12.5
|
64.3
|
57.2
|
Creatinine, mg/dl
|
0.60 (0.52–0.69)
|
0.010
|
1.36
|
52.0
|
74.6
|
AST, U/L
|
0.64 (0.53–0.74)
|
0.010
|
39
|
61.1
|
62.4
|
ALT, U/L
|
0.57 (0.47–0.68)
|
0.151
|
-
|
-
|
-
|
LDH, U/L
|
0.74 (0.64–0.84)
|
< 0.001
|
544
|
71.9
|
72.8
|
Cpk-MB, IU/L
|
0.66 (0.55–0.76)
|
0.004
|
23
|
67.7
|
60.0
|
Cpk, U/L
|
0.61 (0.51–0.71)
|
0.027
|
81.4
|
70.7
|
55.0
|
CRP, mg/l
|
0.61 (0.53–0.68)
|
0.012
|
39.0
|
60.4
|
61.0
|
Esr, mm/h
|
0.55 (0.46–0.64)
|
0.287
|
-
|
-
|
-
|
FBS, mg/dl
|
0.62 (0.53–0.70)
|
0.006
|
179
|
60.0
|
57.0
|
The WBC count had significantly lower predictive ability compared to neutrophil and lymphocyte count. (p < 0.001) Fig. 1
Table 4 presents predictors for poor outcomes of COVID-19 separately, including death, need to ICU care, and invasive mechanical ventilation in diabetic patients based on the results of logistic regression models.
Table 4 Predicting factors for death of the COVID-19 in patients with diabetes mellitus (DM): Logistic Regression Analysis
lass
|
|
Demographic and clinical characteristic
|
Variable
|
Need to ICU
|
Being ventilated during hospitalization
N= 65
|
Death
N= 79
|
Crude OR OR(95% CI)
|
Adjusted§ OR(95% CI)
|
Crude OR OR(95% CI)
|
Adjusted§ OR(95% CI)
|
Crude OR OR(95% CI)
|
Adjusted§ OR(95% CI)
|
Age (≥65/< 65)
|
2.34 (1.48- 3.72)
|
1.72 (1.02-2.94)
|
2.40 (1.38-4.17)
|
2.40 (1.35-4.28)
|
2.44 (1.47-4.05)
|
2.0 (1.16-3.44)
|
Sex (M/F)
|
1.24 (0.79-1.95)
|
-
|
1.42 (0.84-2.41)
|
-
|
1.45 (0.85-2.36)
|
-
|
Comorbidities
|
HTN
|
1.75 (1.10-2.80)
|
-
|
1.15 (0.67-1.96)
|
-
|
1.38 (0.84-2.29)
|
-
|
CVD
|
1.89 (1.21-2.97)
|
-
|
1.86 (1.09-3.19)
|
-
|
1.49 (0.91-2.42)
|
-
|
CKD
|
2.30 (1.41-3.77)
|
-
|
2.58 (1.48-4.52)
|
2.09 (1.16-3.75)
|
2.27 (1.34-3.86)
|
2.05 (1.16 -3.62)
|
Other comorbidity*
|
2.40 (1.26-4.59)
|
-
|
2.42 (1.18-4.96)
|
-
|
2.08 (1.04-4.16)
|
2.20 (1.04-4.63)
|
Number of co. ; Reference category: No comorbidity
|
1
|
1.88 (0.94-3.76)
|
1.61 (0.72-3.60)
|
1.21 (0.52-2.80)
|
-
|
1.14 (0.56-2.33)
|
-
|
2
|
2.61 (1.36-5.0)
|
2.23 (1.04 -4.78)
|
2.42 (1.16-5.06)
|
-
|
1.62 (0.84-3.11)
|
-
|
≥ 3
|
4.80 (2.33-9.88)
|
4.08 (1.78 -9.34)
|
3.46 (1.52-7.83)
|
-
|
2.57 (1.23-5.37)
|
-
|
Drug history
|
ACEIs or ARBs (yes/no)
|
1.70 (1.08-2.67)
|
-
|
1.45 (0.86-2.46)
|
-
|
1.41 (0.86-2.32)
|
-
|
Statins(yes/no)
|
1.76 (1.01-2.76)
|
-
|
1.10 (0.61-1.99)
|
-
|
1.35 (0.78 – 2.35)
|
-
|
Laboratory finding,
|
Hematological, Biochemistry and Isoenzymes parameters
|
WBC, ≥ 8.1/< 8.1(× 10⁹ per L)
|
2.27 (1.41-3.67)
|
-
|
2.56 (1.46-4.47)
|
-
|
2.36 (1.39-3.99)
|
-
|
Lymphocyte, <1.51/ ≥ 1.51 (× 10⁹/L)
|
4.33 (2.60 -7.19)
|
2.28 (1.01-5.15)
|
4.67 (2.59 – 8.47)
|
-
|
5.84 (3.27-10.44)
|
-
|
Neutrophil, ≥ 8.0 / < 8.0 (× 10⁹/L))
|
4.55 (2.74-7.57)
|
2.32 (1.04 -5.24)
|
5.02 (2.82-8.93)
|
5.00 (2.82-8.94)
|
6.65 (3.75-11.80)
|
6.62 (3.73-11.75)
|
Hb, <12.5/ > 12.5(g/dl)
|
2.38 (1.45-3.88)
|
2.03 (1.20-3.43)
|
1.87 (1.04-3.15)
|
-
|
2.21 (1.30 – 3.77)
|
2.05 (1.13-3.72)
|
AST, ≥ 39 / < 39 (U/L)
|
2.32 (1.46-5.46)
|
2.39 (1.12-5.13)
|
2.65 (1.26 -5.61)
|
2.40 (1.25 -5.69)
|
2.62 (1.26-5.44)
|
-
|
Creatinine, ≥1.36/<1.36 (mg/dl)
|
2.57 (1.55-4.24)
|
2.67 (1.25-5.58)
|
2.63 (1.49-4.66)
|
2.64 (1.12-6.21)
|
3.18 (1.83 – 5.53)
|
3.10 (1.38-6.98)
|
CRP, ≥39/<39 (mg/dl)
|
1.65 (0.96-2.81) ‡
|
-
|
1.30 (0.70-2.40)
|
-
|
2.22 (1.25 – 3.94)
|
-
|
FBS, ≥179/<179 (mg/dl)
|
1.72 (1.03 -2.88)
|
-
|
1.63 (0.89-2.95)
|
-
|
1.72 (0.97 – 3.05)
|
-
|
LDH, ≥544/<544(U/L)
|
4.0(1.95-8.17)
|
4.31 (1.36 -13.68)
|
3.74 (1.64-8.49)
|
3.45 (1.36-9.27)
|
7.04 (3.05 -16.26)
|
6.53 (2.51-16.97)
|
Cpk, ≥81.4/<81.4(U/L)
|
2.54 (1.25-5.18)
|
3.67 (0.96-14.23)
|
2.78 (1.23-6.27)
|
-
|
2.44 (1.17-5.09)
|
-
|
Cpk-MB, ≥23/<23(IU/L)
|
3.09 (1.45-6.56)
|
-
|
2.69 (1.12-6.06)
|
-
|
3.18 (1.47 -6.89)
|
-
|
|
†P- value < 0.05 ‡ P- value < 0.20; § in each class, all variables with p < 0.2 in the univariaite model were included in multivariate model.
OR= Odds Ratio. CI= Confidence Interval;
ACEIs= angiotensin-converting enzyme inhibitors. ARBs= angiotensin II receptor blockers. CKD= Chronic Kidney diseases. CVD= Cardiovascular diseases. HTN= Hypertension. ICU= Intensive care unit.
ALT= Alanine transaminases. AST=Aspartate transaminases. CRP=C-reactive protein. CPK= Creatine phosphokinase. CK-MB=creatine kinase myocardial band, Esr= Erythrocyte sedimentation rate. FBS=fasting blood sugar Hb= Hemoglobin. LDH: Lactate dehydrogenase. PT= Prothrombin time. WBC=White blood cell
|
In the multivariate model, significant predictors of “death of COVID-19” were age 65 years or older (OR (95% CI): 2.0 (1.16–3.44), comorbidity CKD (2.05 (1.16–3.62), presence of other comorbidity (2.20 (1.04–4.63)), neutrophil count ≥ 8.0 × 10⁹/L )6.62 (3.73–11.7 ((, Hb level < 12.5 g/dl (2.05 (1.13–3.72)(, and creatinine level ≥ 1.36 mg/dl (3.10 (1.38–6.98)). (All p –values < 0.05)
Patients with age ≥ 65 years, 2 or more comorbidities, lymphocyte count < 1.51 × 10⁹/L, neutrophil count ≥ 8.0 × 10⁹/L, Hb level < 12.5 g/dl, AST level ≥ 39 U/L, creatinine level ≥ 1.36 mg/dl, LDH level ≥ 544 U/L, and Cpk level ≥ 81.4 U/L had significantly higher odds for requiring ICU care than others. (All p –values < 0.05)
Also, patients with age 65 years or older, comorbidity CKD, neutrophil count ≥ 8.0 × 10⁹/L, AST level ≥ 39 U/L, creatinine level ≥ 1.36 mg/dl, LDH level ≥ 544 U/L were more likely to require invasive mechanical ventilation than others. (All p –values < 0.05)
Based on log-rank test results, the difference in the survival distributions between two age groups ≥ 65 years and < 65 years were statistically significant (χ2(1) = 8.73, p = 0.003); but, the differences between males and females did not reach statistical significance (χ2(1) = 2.88, p = 0.09)