Of the 392 COVID-19 patients included during the study period, 233 died (59.4%). The majority of patients were hospitalized at the IMSS (82.4%), 67% were male, the median age was 60 years (range:18-96), the median time between symptom onset and hospital admission was 8 days (range:1-30), and the median hospitalization stay was 9 days (range:0-56), 45.2% of patients were in the fifth category of OSI-WHO (Oxygen by mask or nasal prongs), and approximately 7% of patients had mechanical ventilation or ventilation with organ support/ECMO each (Table 1).
Table 1. Baseline demographic characteristics of the COVID-19 patients, Tapachula, Mexico.
Characteristic
|
Overall
n = 392
|
Alive
n = 159
|
Dead
n= 233
|
p-value
|
Site of attention n (%)
IMSS
COVID Clinic ISSTECH
|
323 (82.4)
69 (17.6)
|
139 (87.4)
20 (12.6)
|
184 (79)
49 (21)
|
0.028
|
Sex Male n (%)
|
263 (67.1)
|
107 (67.3)
|
156 (67)
|
0.943
|
Age years Mean (SD)
|
60 (13)
|
56 (13)
|
63 (12)
|
<0.001
|
Days between symptom onset and admission Median (IQR)
|
8 (5 - 11)
|
8 (6 - 11)
|
7 (5 - 11)
|
0.581
|
Days of hospitalization
|
9 (5 - 16)
|
8 (4 - 14)
|
10 (5 - 16)
|
0.916
|
OSI-WHO Classification n (%)
|
|
|
|
<0.001
|
Hospitalized, no oxygen therapy (4)
|
13 (3.3)
|
11 (6.9)
|
2 (0.9)
|
|
Oxygen by mask or nasal prongs (5)
|
177 (45.2)
|
98 (61.6)
|
79 (33.9)
|
|
Non-invasive ventilation or high-flow oxygen (6)
|
147 (37.5)
|
44 (27.7)
|
103 (44.2)
|
|
Intubation and MV (7a)
|
28 (7.1)
|
3 (1.9)
|
25 (10.7)
|
|
MV + organ support/ECMO (7b)
|
27 (6.9)
|
3 (1.9)
|
24 (10.3)
|
|
Fever n (%)
|
339 (86.5)
|
144 (90.6)
|
195 (83.7)
|
0.046
|
Cough
|
312 (79.6)
|
121 (76.1)
|
191 (82)
|
0.159
|
Dyspneaa
|
309 (79)
|
121 (76.1)
|
188 (81)
|
0.241
|
Myalgia
|
238 (60.7)
|
107 (67.3)
|
131 (56.2)
|
0.027
|
Arthralgia
|
228 (58.2)
|
101 (63.5)
|
127 (54.5)
|
0.075
|
Headache
|
206 (52.6)
|
91 (57.2)
|
115 (49.4)
|
0.125
|
Deterioration of general condition
|
167 (42.6)
|
68 (42.8)
|
99 (42.5)
|
0.956
|
Chest pain
|
115 (29.3)
|
48 (30.2)
|
67 (28.8)
|
0.760
|
Diarrhea
|
87 (22.2)
|
46 (28.9)
|
41 (17.6)
|
0.008
|
Odynophagia
|
87 (22.2)
|
42 (26.4)
|
45 (19.3)
|
0.098
|
Irritability
|
81 (20.7)
|
38 (23.9)
|
43 (18.5)
|
0.193
|
Malaise
|
83 (21.2)
|
43 (27)
|
40 (17.2)
|
0.020
|
Rhinorrhea
|
70 (17.9)
|
31 (19.5)
|
39 (16.7)
|
0.485
|
Dysgeusia/Ageusiab
|
46 (11.8)
|
20 (12.7)
|
26 (11.2)
|
0.653
|
Anosmia
|
46 (11.7)
|
21 (13.2)
|
25 (10.7)
|
0.456
|
Polypnea
|
46 (11.7)
|
18 (11.3)
|
28 (12)
|
0.833
|
Cyanosis
|
18 (4.6)
|
3 (1.9)
|
15 (6.4)
|
0.025
|
Hypertension
|
161 (41.1)
|
60 (37.7)
|
101 (43.4)
|
0.267
|
Diabetes
|
157 (40.1)
|
54 (34)
|
103 (44.2)
|
0.041
|
Chronical kidney disease
|
30 (7.7)
|
9 (5.7)
|
21 (9)
|
0.212
|
aThere was one missing value in death patients (n=232).
bThere was one missing value in alive patients (n=158).
Fever, cough and dyspnea were the most frequent symptoms, followed by nonspecific symptoms like myalgia, arthralgia, and headache. Upper respiratory symptoms including odynophagia, rhinorrhea, dysgeusia and anosmia were observed less frequently. Symptoms such as abdominal pain, hyporexia, vomit, nausea, dizziness, conjunctivitis, prechordalgia, polypnea, and cyanosis were observed in less than 10% of participants. Hypertension was the most frequent comorbidity, followed by diabetes mellitus and chronical kidney disease. Conditions such as gastrointestinal (4.3%), lung (3.6%), cardiovascular (3.6%), neurological (1.3%), and endocrine diseases (1%), cancer (2%) and stroke (1.5%) were infrequent (Table 1). The leukocyte count geometric mean was 11.9x103/cc with predominance of neutrophils, creatinine and lactate dehydrogenase (LDH) geometric means were above normal values with 1.3 mg/ml and 515 UI/L, respectively (Table 1). During hospitalization, most patients were treated with antibiotics, while steroids were only used in 20.2% of the patients (Table 2).
Table 2. Baseline blood test results and treatment of the COVID-19 patients, Tapachula, Mexico.
Characteristic
|
n
|
Overall
n = 392
|
Alive
n = 159
|
Dead
n= 233
|
p-value
|
Hemoglobin GMT (LCL-UCL)
|
144/203
|
12.8 (12.6 - 13.1)
|
12.9 (12.5 - 13.4)
|
12.8 (12.5 - 13.1)
|
0.052
|
Red cell distribution width
|
140/198
|
14.3 (14.0 - 14.6)
|
13.9 (13.7 - 14.1)
|
14.6 (14.1 - 15.1)
|
<0.001
|
Leukocyte count x 103/cc
|
144/203
|
11.9 (11.4 - 12.5)
|
10.6 (9.9 - 11.4)
|
13.0 (12.1 - 13.8)
|
<0.001
|
Neutrophil count x 103/cc
|
144/202
|
10.0 (9.4 - 10.6)
|
8.6 (7.9 - 9.3)
|
11.1 (10.3 - 11.9)
|
<0.001
|
Lymphocyte count x 103/cc
|
144/202
|
0.67 (0.61 - 0.73)
|
0.86 (0.77 - 0.96)
|
0.56 (0.50 - 0.63)
|
<0.001
|
NT/LYN ratio
|
144/201
|
15 (13 - 17)
|
10 (9 - 12)
|
20 (17 - 23)
|
<0.001
|
Platelet count x 103/cc
|
144/203
|
271 (258 - 284)
|
283 (265 - 303)
|
262 (245 - 280)
|
0.13
|
Prothrombin time sec.
|
114/174
|
13.2 (13.0 - 13.4)
|
12.9 (12.6 -13.1)
|
13.5 (13.2 - 13.8)
|
<0.001
|
Activated partial thromboplastin time sec.
|
112/170
|
34 (33 - 35)
|
33 (32 - 35)
|
34 (33 - 36)
|
0.4
|
INR
|
114/174
|
1.12 (1.11-1.14)
|
1.09 (1.06-1.11)
|
1.15 (1.13-1.18)
|
<0.001
|
Glycemia mg/dL
|
135/195
|
156 (146 - 167)
|
139 (126 - 153)
|
170 (155 - 185)
|
<0.001
|
Urea mg/dL
|
132/192
|
47 (43 - 52)
|
36 (32 - 42)
|
56 (50 - 63)
|
<0.001
|
Creatinine mg/ml
|
134/193
|
1.3 (1.1 - 1.4)
|
1.0 (0.9 - 1.2)
|
1.5 (1.3 - 1.7)
|
<0.001
|
LDH UI/L
|
128/176
|
515 (487 - 545)
|
432 (400 - 467)
|
585 (543 - 631)
|
<0.001
|
Total bilirubin mg/ml
|
134/186
|
0.64 (0.60 - 0.68)
|
0.64 (0.58 - 0.71)
|
0.64 (0.59 - 0.69)
|
>0.9
|
ALT UI/L
|
135/192
|
49 (45 - 53)
|
47 (42 - 52)
|
50 (45 - 56)
|
0.6
|
AST UI/L
|
135/191
|
42 (38 - 45)
|
45 (40 - 51)
|
39 (35 - 44)
|
0.017
|
Albumin g/dL
|
122/162
|
3.0 (2.9 - 3.1)
|
3.2 (3.0 - 3.3)
|
2.9 (2.8 - 3.0)
|
<0.001
|
Sodium mEq/L
|
127/180
|
134 (133 - 135)
|
135 (134 - 136)
|
134 (133 - 135)
|
>0.9
|
Potassium mmol/L
|
132/196
|
4.3 (4.2 - 4.4)
|
4.3 (4.1 - 4.4)
|
4.4 (4.3 - 4.5)
|
0.11
|
Chlorine mEq/L
|
132/196
|
98 (96 - 100)
|
100 (99 - 101)
|
96 (93 - 100)
|
0.14
|
Any antibiotic n%
|
155/226
|
335 (87.9)
|
135 (87.1)
|
200 (88.5)
|
0.681
|
Ceftriaxone (CFT)
|
155/226
|
280 (73.5)
|
117 (75.5)
|
163 (72.1)
|
0.464
|
Azithromycin (AZT)
|
155/226
|
264 (69.3)
|
108 (69.7)
|
156 (69)
|
0.892
|
AZT and CFT
|
155/226
|
221 (58)
|
92 (59.4)
|
129 (57.1)
|
0.658
|
Steroid
|
155/226
|
77 (20.2)
|
29 (18.7)
|
48 (21.2)
|
0.545
|
In the univariate analysis, a significant difference between patients who died and those who survived was observed for the following variables: site, age, OSI-WHO classification, diabetes, and symptoms such as fever, myalgia, diarrhea, malaise, and cyanosis (Table 1). In addition, the red cell distribution width, leukocyte count, neutrophil count, prothrombin time, international normalized ratio (INR), glycemia, serum urea, serum creatinine, and LDH geometric means were higher in patients who died. Conversely, the lymphocyte count and aspartate aminotransferase (AST) geometric means were lower in this group (Table 2).
The death frequency was similar by sex (p-value=0.943) (Table 1, Figure 1). Malaise, polypnea and cyanosis were more frequent in women (p<0.05), while neutrophil count (p=0.035), Neutrophil/Lymphocyte (NT/LY) ratio (p<0.001), urea (p=0.01), creatinine (p=0.003), total bilirubin (p<0.001), the aminotransferases (p<0.001), and the potassium (p=0.02) geometric means were lower in women (Supplementary Table 1). Patients of this clinical cohort had a greater diabetes prevalence than the overall Mexican and Chiapas populations, and men had a greater hypertension prevalence (Supplementary Table 2).
The numbers above the bars represent the percentage of participants who died in each OSI-WHO classification group by sex. The percentage of death increases according to OSI-WHO classification in women and men.
The time between symptom onset and admission were not related to death (p=0.581), with median time between symptom onset and admission of 8 days in survived patients, and 7 days in participants who died. However, the lethality was different between the sites (p=0.032), and there was a significant difference observed in OSI/WHO classification between sites (p=<0.001) (Supplementary Table 3).
Three multivariate logistic regression models were developed to predict death (training set, n=276). Age, diarrhea, LDH, AST, and the lymphocyte count were present in the three models, while OSI-WHO classification, leukocyte count and NT/LYN ratio were variables selected in two models, and diabetes, platelet count and red cell distribution only selected in one model (Table 3).
Table 3. Predictive models for COVID-19 death using logistic regression (training set: 70% of patients).
Characteristic
|
OR
(95%CI)
|
M1
ORa (95%CI)
|
M1a
ORa (95%CI)
|
M2
ORa (95%CI)
|
Age
|
1.04 (1.02- 1.06)
|
1.04 (1.02 - 1.07)
|
1.04 (1.02 - 1.07)
|
1.05 (1.02 - 1.07)
|
OSI-WHO Classification
|
|
|
|
|
Hospitalized, no oxygen therapy (4)
|
Ref.
|
Ref.
|
Ref.
|
|
Oxygen by mask or nasal prongs (5)
|
5.97 (1.02 – 113)
|
4.67 (0.92 - 36.24)
|
4.14 (0.83-32.60)
|
|
Non-invasive ventilation or high-flow oxygen (6)
|
16.2 (2.73 – 309)
|
8.8 (1.66 - 69.87)
|
8.53 (1.65-68.70)
|
|
Intubation and MV (7a)
|
112 (9.48 – 4,403)
|
26.92 (3.29-324.38)
|
32.15 (3.93-398.0)
|
|
MV + organ support/ECMO (7b)
|
59.5 (6.50 – 1,511)
|
22.41 (2.63-276.85)
|
20.08 (2.46-242.46)
|
|
Diarrhea
|
0.47 (0.26 – 0.85)
|
0.496 (0.24 - 1.01)
|
0.55 (0.27 - 1.10)
|
0.44 (0.22 - 0.85)
|
Diabetes
|
2.05 (1.23 – 3.46)
|
1.97 (1.05 - 3.78)
|
|
|
Log 2 LDH UI/L
|
2.33 (1.52 – 3.74)
|
2.95 (1.66 - 5.49)
|
3.05 (1.78 - 5.51)
|
4.35 (2.63 - 7.60)
|
Log 2 AST UI/L
|
0.77 (0.60 – 0.98)
|
0.58 (0.42 - 0.81)
|
0.54 (0.40 - 0.74)
|
0.58 (0.43 - 0.77)
|
Log2 Lymphocyte
|
0.62 (0.47 – 0.81)
|
0.495 (0.31 - 0.82)
|
0.50 (0.32 - 0.79)
|
0.55 (0.41 - 0.72)
|
Log2 Leukocyte count
|
1.69 (1.14 – 2.55)
|
1.94 (1.10 - 3.44)
|
1.77 (1.03 - 3.01)
|
|
NT/LYN ratio
|
1.02 (1.01 -1 1.04)
|
0.99 (0.98 - 1.01)
|
0.99 (0.98 - 1.01)
|
|
Log2 Platelet count
|
0.62 (0.40 - 0.92)
|
0.70 (0.42 - 1.17)
|
|
|
Log 2 Red cell distribution width
|
7.11 (1.36 – 55.2)
|
7.66 (1.13 - 87.66)
|
|
|
Site of attention
IMSS
COVID Clinic ISSTECH
|
Ref.
1.46 (0.77 - 2.86)
|
Ref.
0.83 (0.26 - 2.67)
|
Ref.
0.68 (0.23 - 2.0)
|
Ref.
0.78 (0.29 - 2.17)
|
The M1a model had the highest sensitivity in the training set (n=276), however the AUCs (Figure 2) were similar among the three models (≈0.8). The M1 model had the highest sensitivity in the test set (n=116) with no difference in the AUC among the three models (Table 4). Focusing on M1, we found an association between the OSI-WHO classification and the risk of death, with higher odds of a participant dying for participants wit non-invasive ventilation or high-flow oxygen, intubation or on mechanical ventilation, and mechanical ventilation or ECMO (when compared to no oxygen therapy). We found higher odds of death for participants with diabetes mellitus, increases in Log2 LDH, and Log2 Leukocyte count, and lower odds of death with increases in in Log2 AST and Log2 Lymphocytes (Table 3).
Table 4. Model performance in treating set (Tr, n=276) and test set (T, n=116).
Model
|
Accuracy
|
Sensitivity
|
Specificity
|
PPV
|
NPV
|
AUC (95%CI)
|
Model M1 (Tr)
|
0.756
|
0.792
|
0.706
|
0.792
|
0.706
|
0.807 (0.745 - 0.869)
|
Model M1a (Tr)
|
0.761
|
0.825
|
0.671
|
0.780
|
0.731
|
0.806 (0.744 - 0.868)
|
Model M2 (Tr)
|
0.751
|
0.783
|
0.706
|
0.790
|
0.698
|
0.791 (0.726 - 0.856)
|
Model M1 (T)
|
0.762
|
0.818
|
0.700
|
0.750
|
0.778
|
0.764 (0.671 - 0.857)
|
Model M1a (T)
|
0.744
|
0.737
|
0.759
|
0.857
|
0.595
|
0.726 (0.632 - 0.820)
|
Model M2 (T)
|
0.767
|
0.774
|
0.758
|
0.837
|
0.676
|
0.756 (0.664 - 0.849)
|