Demographics and baseline characteristic of young adults with severe COVID-19
From 25 Jan 2020 to 15 Feb 2020, 376 patients were admitted to Tongji hospital with confirmed COVID-19, of whom 299 were considered ineligible. 77 young adults with severe COVID-19 were included in this study (Supplement Figure 1). Baseline characteristics of patients were divided into subgroups by survival or non-survival (Table 1). Different from all-age populations, there were no significant difference in age and sex among young adults with severe COVID-19 (Supplement table 1). Patients in non-survivor group were with faster heart rate than survival group. Other characteristics such as exposure history, smoking history, comorbidities, respiratory rate, percutaneous oxygen saturation, blood pressure showed no significance between two groups.
Table 1. Demographics and baseline characteristic of young adults with severe COVID-19.
|
Total
n = 77
|
Survivor
n = 37
|
Non-survivor
n = 40
|
P value
|
Age, years
|
59
(54-63)
|
58
(50-62)
|
60
(57-64)
|
0.077
|
Sex (male)
|
50 (65%)
|
21 (57%)
|
29 (73%)
|
0.148*
|
Exposure history
|
10 (13%)
|
5 (14%)
|
5 (13%)
|
0.895*
|
Smoker
|
3 (4%)
|
2 (6%)
|
1 (3%)
|
0.981*
|
Comorbidity
|
72 (94%)
|
35 (95%)
|
97 (93%)
|
1*
|
Hypertension
|
26
(34%)
|
12
(33%)
|
414 (35%)
|
0.812*
|
Diabetes
|
9 (12%)
|
5 (14%)
|
4 (10%)
|
0.901*
|
Coronary heart disease
|
3 (4%)
|
0 (0)
|
3 (8%)
|
0.241*
|
Malignancy
|
2 (3%)
|
2 (6%)
|
0 (0)
|
0.228*
|
Chronic kidney disease
|
2 (3%)
|
0 (0)
|
2 (5%)
|
0.494*
|
Tuberculosis
|
1 (1%)
|
0 (0)
|
1 (3%)
|
1*
|
Chronic hepatitis B
|
4 (5%)
|
2 (5%)
|
2 (5%)
|
1*
|
Others
|
28 (36%)
|
14 (38%)
|
14 (35%)
|
0.796*
|
Respiratory rate, >30 breath per min
|
13/75
(17%)
|
4/37 (11%)
|
9/40
(24%)
|
0.141*
|
Heart rate, ≥125 beats per min
|
7/76
(9%)
|
0/36
(0)
|
7/40 (18%)
|
0.012*
|
Percutaneous oxygen saturation, ≤93%
|
55 (71%)
|
25 (68%)
|
30 (75%)
|
0.471
|
Systolic pressure, mmH
|
131
(119-146)
|
130
(114-142)
|
132
(121-151)
|
0.582
|
Diastolic pressure, mmHg
|
79
(67-85)
|
76
(62-85)
|
80
(71-88)
|
0.185
|
Fever
|
72 (94%)
|
35 (95%)
|
37 (93%)
|
1*
|
Sore throat
|
4 (5%)
|
2(5%)
|
2 (5%)
|
1*
|
Cough
|
59 (77%)
|
27 (73%)
|
32 (80%)
|
0.467*
|
Chest pain
|
3 (4%)
|
1 (3%)
|
2 (5%)
|
1*
|
Dyspnea
|
51 (66%)
|
18 (49%)
|
33 (83%)
|
0.002*
|
Fatigue
|
42 (55%)
|
20 (54%)
|
22 (55%)
|
0.834*
|
Myalgia
|
14 (18%)
|
8 (22%)
|
6 (15%)
|
0.452*
|
Nausea or vomiting
|
5 (7%)
|
1 (3%)
|
4 (10%)
|
0.403*
|
Diarrhea
|
25 (33%)
|
12 (33%)
|
13 (33%)
|
0.995*
|
Stomachache
|
5 (5%)
|
1 (3%)
|
4 (10%)
|
0.403*
|
Headache
|
7 (9 %)
|
3 (8%)
|
5 (10%)
|
1*
|
Unconscious
|
2 (3%)
|
0 (0)
|
2 (5%)
|
0.494*
|
Dizziness
|
3 (4%)
|
0 (0)
|
3 (8%)
|
0.241*
|
Data are median (IQR), n (%), or n/N (%). p values were calculated by Mann-Whitney U test, χ² test, or Fisher’s exact test, as appropriate. *χ² test comparing all subcategories
Similar to the results reported in previous researches, we pointed out that the top four symptoms included fever (94%), cough (77%), dyspnea (66%), fatigue (55%) in hospital among all-age population (Table 1, Supplement table 2).(1, 12) Except for dyspnea that were more often present in non-survivor group than survivor group (83% vs. 49%), other symptoms were comparable in two groups. But in all-age patients, incidence of unconscious and dizziness were higher in non-survivors than that of survivors.
Laboratory findings
The non-survivors had more white blood cells and neutrophils counts than that of the survivors, may result from the presence of secondary bacterial infection as indicated by higher concentrations of hs-CRP and procalcitonin (Table 2, Supplement table 3). As expected, the non-survivors had reduced lymphocytes. Compared with survivors, those in non-survivor group underwent susceptible to abnormalities of liver, kidney and coagulation function, suggested by elevation of albumin or creatinine, and dysregulation of d-dimer. The non-survivors had experienced more frequently and severe heart injury, as all laboratory heart function parameters including hs-CTnl, myoglobin, and N-terminal pro-brain natriuretic peptide (NT-proBNP), were all significantly increased. The similar results had been shown in all-age patients.
Table 2. Laboratory examinations of young adults with severe COVID-19.
Findings (normal range)
|
Total
n = 77
|
Survivor
n = 37
|
Non-survivor
n = 40
|
P value
|
Blood routine test
|
|
|
|
|
White blood cell, x109/L (3.5-9.5)
|
7.5
(5.9-10.6)
|
6.5
(4.7-8.4)
|
9.7
(7.1-13.0)
|
<0.001
|
Neutrophil granulocyte, x109/L (1.8-6.3)
|
6.6
(4.2-9.7)
|
5.0
(3.6-6.7)
|
8.8
(5.9-12.0)
|
<0.001
|
Lymphocyte, x109/L (1.1-3.2)
|
0.7
(0.5-1.0)
|
0.9
(0.7-1.2)
|
0.6
(0.4-0.7)
|
<0.001
|
Red blood cell, x109/L (3.8-5.1)
|
4.2
(3.7-4.6)
|
4.2
(3.7-4.4)
|
4.2
(3.7-4.8)
|
0.383
|
Haemoglobin, g/L (130-175)
|
129
(115-140)
|
129
(118-136)
|
130
(111-143)
|
0.665
|
Platelet, x109/L (125-350)
|
194
(148-128)
|
201
(162-279)
|
153
(127-244)
|
0.092
|
Coagulation function
|
|
|
|
|
PT, s (11.5-14.5)
|
14.9
(13.8-16.3)
|
13.8
(13.3-14.6)
|
15.7
(15.1-17.2)
|
<0.001
|
APTT, s (29.0- 42.0)
|
39.9
(36.2-44.9)
|
40.5
(37.1-44.8)
|
39.4
(34.4-45.0)
|
0.468
|
D-dimer, ug/ml (<0.5)
|
2.4
(1.0-21.0)
|
1.3
(0.7-2.2)
|
18.2
(3.0-21.0)
|
<0.001
|
Biochemical test
|
|
|
|
|
Albumin, g/L (35.0-52.0)
|
31.1
(28.5-35.0)
|
32.8
(20.2-36.3)
|
30.0
(27.2-33.7)
|
0.001
|
Globulin, g/L (20.0-35.0)
|
34.6
(31.5-37.9)
|
33.6
(31.1-36.8)
|
35.5
(31.6-39.2)
|
0.172
|
Aspartate
aminotransferase, U/L
(≤40)
|
34 (23-52)
|
30 (20-46)
|
37 (28-57)
|
0.296
|
Alanine aminotransferase, U/L (≤41)
|
29 (20-50)
|
28 (20-57)
|
29 (18-48)
|
0.721
|
Total-bilirubin, umol/L (≤26)
|
10.1
(7.5-14.9)
|
8.6
(6.7-11.7)
|
12.2
(8.4-19.2)
|
0.002
|
Direct-bilirubin, umol/L (≤8)
|
4.9
(3.5-7.4)
|
3.6
(3.3-5.1)
|
6.4
(4.5-10.2)
|
<0.001
|
Creatinine, umol/L (59-104)
|
70 (55-87)
|
64 (50-82)
|
78 (59-99)
|
0.024
|
Urea nitrogen, mmol/L (3.1-8.0)
|
5.3
(3.5-7.2)
|
3.7
(2.9-5.2)
|
7.0
(5.3-9.4)
|
<0.001
|
LDH, U/L (135-225)
|
460
(347-585)
|
359
(268-456)
|
567
(475-663)
|
0.442
|
Infection-related biomarkers
|
|
|
|
|
Procalcitonin, ng/mL (0.02-0.05)
|
0.13
(0.04-0.29)
|
0.04
(0.02-0.13)
|
0.23
(0.14-0.60)
|
<0.001
|
ERS, mm/h (0-15)
|
35 (20-64)
|
34 (20-71)
|
37 (20-54)
|
0.586
|
Ferritin, ng (30-400)
|
1336
(685-2020)
|
1113
(374-1605)
|
1701
(995-3113)
|
0.032
|
hs-CRP, mg/L (<1)
|
72.5
(38.3-140.2)
|
52.1
(28.4-88.4)
|
120
(55.9-183.0)
|
<0.001
|
Myocardial enzymes
|
|
|
|
|
Creatine kinase, U/L (≤190)
|
116
(54-308)
|
100
(42-212)
|
119
(61-397)
|
0.442
|
NT-BNP, pg/mL (<285)
|
292
(87-852)
|
87
(39-205)
|
709
(300-1773)
|
<0.001
|
hs-CTnl, pg/mL (≤15.6)
|
13.0
(3.4-111.3)
|
3.6
(2.1-10.1)
|
41.5
(12.1-308.6)
|
<0.001
|
Myoglobin, ng/mL (≤106)
|
131
(29-324)
|
29
(21-123)
|
258
(130-470)
|
0.001
|
Abbreviation: PT, prothrombin time; APTT, activated partial thromboplastin time; LDH, Lactate dehydrogenase; ERS, erythrocyte sedimentation rate; hs-CRP, high sensitivity C-reactive protein; NT-proBNP, N-terminal pro-brain natriuretic peptide; hs-CTnI, hypersensitive cardiac troponin I. Data are median (IQR), n (%), or n/N (%). p values were calculated by Mann-Whitney U test, χ² test, or Fisher’s exact test, as appropriate. *χ² test comparing all subcategories.
Treatment and outcomes
More than half non-survivors experienced mechanical ventilation and ICU admission (Table 3, Supplement table 4). The median time from illness onset to death was 24 days (IQR 6–17), whereas the median time from illness onset to discharge was 38 days (IQR 21–33). The similar trend was shown in hospital length of stay (11 [IQR 6-17] vs. 25 [IQR 21-33]). Consistent with discharge standers, viral shedding of survivors was happened during treatment course.
Table 3 Treatment and outcomes of young adults with severe COVID-19.
|
Total
n = 77
|
Survivor
n = 37
|
Non-survivor
n = 40
|
P value
|
Treatment
|
|
|
|
|
High-flow nasal cannula oxygen therapy
|
15 (20%)
|
6
(16%)
|
9
(23%)
|
0.487*
|
Non-invasive mechanical ventilation
|
28 (36%)
|
2
(5%)
|
26 (65%)
|
<0.001*
|
Invasive mechanical ventilation
|
27 (35%)
|
0
(0)
|
27 (68%)
|
<0.001*
|
ECMO
|
2 (3%)
|
0 (0)
|
2 (5%)
|
0.494*
|
Outcomes
|
|
|
|
|
ICU admission
|
29 (38%)
|
1
(3%)
|
28 (70%)
|
<0.001*
|
ICU length of stay, days
|
10
(4-19)
|
..
|
10
(4-17)
|
..
|
Hospital length of stay, days
|
19
(11-27)
|
25
(21-33)
|
11
(6-17)
|
<0.001
|
Time from illness onset to ICU admission, days
|
16
(13-20)
|
..
|
16
(13-21)
|
..
|
Time from illness onset to death or discharge, days
|
30
(22-39)
|
38
(32-45)
|
24
(19-29)
|
<0.001
|
SARS-CoV-2 RT-PCR test (-)
|
43/77 (56%)
|
35/37 (95%)
|
8/40 (20%)
|
<0.001*
|
Duration of viral shedding after COVID-19 onset, days
|
22
(18-27)
|
23
(19-28)
|
19
(15-24)
|
0.054
|
Abbreviation: ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; RT-PCR, real-time polymerase chain reaction. Data are median (IQR), n (%), or n/N (%). P values were calculated by χ² test, or Fisher’s exact test, as appropriate. *χ² test comparing all subcategories.
Predictors of mortality
All demographic data, clinical symptoms, laboratory findings, treatments and outcomes were shown in Table 1 and Table 2, we evaluated every variable that demonstrated statistical significance with p < 0.05 between non-survivor and survivor groups by univariate logistic regression analysis (Table 4).Slightly different from all-age population, white blood cell, neutrophil granulocyte, lymphocyte, prothrombin time, d-dimer, albumin, direct-bilirubin, urea nitrogen, procalcitonin, hs-CRP, NT-proBNP and hs-CTnl were associated with the risk of mortality (Supplement table 5).
Table 4 Univariate logistic regression analysis of mortality risk factors in young adults with severe COVID-19.
Factor
|
Univariable OR
(95% CI)
|
P value
|
White blood cell >9.5 x109/L, %
|
5.167 (1.716-15.087)
|
0.003
|
Neutrophil granulocyte >6.3 x109/L, %
|
7.118 (2.608-19.428)
|
<0.001
|
Lymphocyte <0.5 x109/L, %
|
9.273 (2.441-35.227)
|
0.001
|
PT >14.5s, %
|
21.778 (6.554-72.367)
|
<0.001
|
D-dimer >21μg/mL, %
|
34.200 (4.256-274.808)
|
0.001
|
Albumin <30g/L, %
|
7.143 (2.519-20.257)
|
<0.001
|
Direct-bilirubin >8umol/L
|
5.457 (1.410-21.117)
|
0.014
|
Urea nitrogen >8mmol/L
|
4.857 (1.246-18.933)
|
0.023
|
Procalcitonin >0.05ng/mL, %
|
19.559 (4.077-93.825)
|
<0.001
|
hs-CRP >100mg/L, %
|
5.955 (2.098-16.904)
|
0.001
|
NT-proBNP ≥285pg/ml, %
|
18.000 (5.211-62.176)
|
<0.001
|
hs-CTnI >15.6pg/ml, %
|
16.667 (4.234-65.601)
|
<0.001
|
Abbreviation: OR, odds ratio; PT, prothrombin time; hs-CRP, high sensitivity C-reactive protein; NT-proBNP, N-terminal pro-brain natriuretic peptide; hs-CTnI, hypersensitive cardiac troponin I.
Multivariate logistic regression analyses were applied to assess the independent prognostic effect of related factors (Table 5). Before adjusting other variables, odds ratio (OR) of lymphocyte <0.5 X109/L, d-dimer >21μg/mL and hs-CTnI >15.6pg/ml were 7.03 (95% CI 1.435-40.275), 11.012 (95% CI 1.092-111.100) and 13.876 (95% CI 2.888-66.673). When adjusting for other variables, the OR of above three fixed variables changed slightly. According to the AIC level of each model (Supplement table 6), we chose the lowest AIC level as the best. The multivariate logistic regression analyses model 5 including lymphocyte <0.5 X109/L, d-dimer >21μg/mL, hs-CTnI >15.6pg/ml and hs-CRP >100mg/L (Table 5, mode 5), were the best predictors of mortality.
Table 5 Multivariate logistic regression analysis of mortality risk factors in young adults with severe COVID-19.
Mode
|
Multivariable
OR (95% CI)
|
P value
|
Mode 1
|
|
|
Lymphocyte <0.5 x109/L, %
|
7.03 (1.435-40.275)
|
0.017
|
D-dimer >21μg/mL, %
|
11.012 (1.092-111.100)
|
0.042
|
hs-CTnI >15.6pg/ml, %
|
13.876 (2.888-66.673)
|
0.001
|
Mode 2
|
|
|
Lymphocyte <0.5 x109/L, %
|
6.496 (1.182-35.709)
|
0.031
|
D-dimer >21μg/mL, %
|
8.382 (0.770-91.279)
|
0.081
|
hs-CTnI >15.6pg/ml, %
|
14.140 (2.864-69.817)
|
0.001
|
White blood cell >9.5 x109/L, %
|
2.883 (0.611-13.604)
|
0.181
|
Mode 3
|
|
|
Lymphocyte <0.5 x109/L, %
|
5.639 (1.027-30.958)
|
0.047
|
D-dimer >21μg/mL, %
|
6.556 (0.624-68.908)
|
0.117
|
hs-CTnI >15.6pg/ml, %
|
14.228 (2.841-71.252)
|
0.001
|
Neutrophil granulocyte >6.3x109/L, %
|
3.173 (0.712-14.129)
|
0.130
|
Mode 4
|
|
|
Lymphocyte <0.5 x109/L, %
|
6.560 (1.161-37.067)
|
0.033
|
D-dimer >21μg/mL, %
|
5.306 (0.490-57.501)
|
0.170
|
hs-CTnI >15.6pg/ml, %
|
8.860 (1.730-45.366)
|
0.009
|
PT >14.5s, %
|
4.719 (0.997-22.326)
|
0.050
|
Mode 5
|
|
|
Lymphocyte <0.5 x109/L, %
|
9.191 (1.190-70.996)
|
0.033
|
D-dimer >21μg/mL, %
|
24.142 (1.622-359.302)
|
0.021
|
hs-CTnI >15.6pg/ml, %
|
10.358 (1.711-63.036)
|
0.011
|
hs-CRP >100mg/L, %
|
19.528 (3.068-124.288)
|
0.022
|
Mode 6
|
|
|
Lymphocyte <0.5 x109/L, %
|
6.790 (1.242-37.129)
|
0.027
|
D-dimer >21μg/mL, %
|
7.964 (0.702-90.402)
|
0.094
|
hs-CTnI >15.6pg/ml, %
|
13.129 (2.668-64.599)
|
0.002
|
Albumin <30g/L, %
|
2.900 (0.660-12.746)
|
0.159
|
Mode 7
|
|
|
Lymphocyte <0.5 x109/L, %
|
7.598 (1.434-40.249)
|
0.017
|
D-dimer >21μg/mL, %
|
10.575 (0.752-148.749)
|
0.080
|
hs-CTnI >15.6pg/ml, %
|
13.942 (2.878-67.526)
|
0.001
|
Direct-bilirubin >8umol/L
|
1.070 (0.121-9.442)
|
0.952
|
Mode 8
|
|
|
Lymphocyte <0.5 x109/L, %
|
8.684 (1.507-50.054)
|
0.016
|
D-dimer >21μg/mL, %
|
11.719 (1.086-126.460)
|
0.043
|
hs-CTnI >15.6pg/ml, %
|
13.209 (2.609-66.883)
|
0.002
|
Urea nitrogen >8mmol/L
|
4.233 (0.479-37.407)
|
0.194
|
Mode 9
|
|
|
Lymphocyte <0.5 x109/L, %
|
3.796 (0.671-21.481)
|
0.131
|
D-dimer >21μg/mL, %
|
16.923 (0.990-289.353)
|
0.051
|
hs-CTnI >15.6pg/ml, %
|
9.509 (1.833-49.323)
|
0.007
|
Procalcitonin >0.05ng/mL, %
|
9.876 (0.926-105.342)
|
0.058
|
Mode 10
|
|
|
Lymphocyte <0.5 x109/L, %
|
7.412 (1.205-45.602)
|
0.031
|
D-dimer >21μg/mL, %
|
4.625 (0.446-47.978)
|
0.199
|
hs-CTnI >15.6pg/ml, %
|
7.589 (1.360-42.335)
|
0.021
|
NT-proBNP ≥285pg/ml, %
|
7.011 (1.452-33.843)
|
0.015
|
Abbreviation: OR, odds ratio; PT, prothrombin time; hs-CRP, high sensitivity C-reactive protein; NT-proBNP, N-terminal pro-brain natriuretic peptide; hs-CTnI, hypersensitive cardiac troponin I.
According to the level of four variables in mode 5, we classified of young adults with severe COVID-19 to low-risk and high-risk subgroups. The cumulative survival rate of low-risk group was much higher than that of high-risk group (Figure 1). The same predictive effect of four factors were shown in all-age participants with severe COVID-19.