Demographic information of COVID-19 hospitalized patients
Total of 140 adult patients confirmed severe COVID-19 in wards from designated hospital was enrolled in this research, 73 patients were with identification of influenza virus IgM-positive and 67 patients were with influenza virus IgM-negative. Nearly half of severe COVID-19 patients in this research are male. The median age of patients with influenza virus-IgM negative was 66 years (interquartile range [IQR], 55 to 70 years), a litter older than the median age of patients with influenza virus IgM-positive (median age 62, interquartile range [IQR], 47 to 70 years), with an equal gender distribution. Majority of the severe COVID-19 patients had chronic underlying conditions consisting mainly of hypertension, diabetes, chronic respiratory disease, malignancy and chronic kidney disease. The demographic information was showed in Table 1.
Table 1
Clinical Characteristics of COVID-19 Patients with and Without Influenza IgM positive.
Study Population
|
With Influenza
IgM positive
No. (%) (n = 73)
|
Without Influenza
IgM positive
No. (%) (n = 67)
|
P value
|
Demophrafic
|
|
|
|
Gender, Male
|
39(53.4%)
|
37(55.2%)
|
0.831
|
Age, median (IQR), yrs
|
62(47,70)
|
66(55,70)
|
0.112
|
Comorbidities
|
|
|
|
Chronic respiratory disease
|
5(6.9%)
|
5(7.5%)
|
1.000
|
Malignancy
|
3(4.2%)
|
3(4.5%)
|
1.000
|
Hypertension
|
34(45.7%)
|
30(44.8%)
|
0.912
|
Diabetes
|
12(16.7%)
|
10(14.9%)
|
0.779
|
Cardiovascular disease
|
5(6.9%)
|
3(4.5%)
|
0.720
|
Chronic kidney disease
|
2(2.8%)
|
1(1.5%)
|
1.000
|
Signs and symptoms
|
|
|
|
Fever
|
55(75.3%)
|
53(79.1%)
|
0.596
|
Highest temperature, °C
|
38.5(38.0,39.0)
|
38.7(38.2–39.0)
|
0.127
|
Chills
|
13(17.8%)
|
19(28.4%)
|
0.161
|
Cough
|
41(56.9%)
|
44(65.7%)
|
0.292
|
Productive cough
|
20(27.8%)
|
25(37.3%)
|
0.230
|
Chest pain/Chest congestion
|
19(26.4%)
|
13(19.4%)
|
0.328
|
Wheeze
|
19(26.4%)
|
6(9.0%)
|
0.008*
|
Dyspnea
|
21(29.2%)
|
29(43.3%)
|
0.083
|
Diarrhea
|
18(24.7%)
|
25(37.3%)
|
0.105
|
Fatigue or myalgia
|
28(38.4%)
|
39(58.2%)
|
0.019*
|
Laboratory findings, median (IQR)
|
|
|
|
White blood cells, ×109/mL
|
5.65(4.23–6.88)
|
5.67(4.54–7.95)
|
0.323
|
Neutrophils, ×109/mL
|
3.86(2.47–4.82)
|
3.98(2.54–5.93)
|
0.360
|
Lymphocytes, ×109/mL
|
1.21(0.82–1.61)
|
1.08(0.77–1.53)
|
0.383
|
Lymphocytes < 0.8 × 109/mL
|
18 (24.7%)
|
18 (27.3%)
|
0.847
|
Red blood cells, ×1012/mL
|
4.10(3.62–4.58)
|
4.04(3.67–4.43)
|
0.450
|
Platelets, ×109/ mL
|
230(169–299)
|
253(166–343)
|
0.362
|
PLT < 100 × 109/ mL
|
5 (6.8%)
|
6 (9.1%)
|
0.756
|
Hemoglobin, g/L
|
122(114–138)
|
126(113–138)
|
0.914
|
ALT, U/L
|
23(17–41)
|
23(15–41)
|
0.737
|
AST, U/L
|
26(19–38)
|
30(19–41)
|
0.337
|
Albumin, g/L
|
36(32–38)
|
35(31–37)
|
0.295
|
Creatinine, µmol/L
|
70(60–90)
|
70(59–88)
|
0.860
|
eGFR
|
93.06 (75.8-106.8)
|
90.28 (70.6–98.9)
|
0.338
|
eGFR < 60
|
8 (11.1%)
|
9 (13.6%)
|
0.797
|
LDH, U/L
|
269(203–330)
|
287(235–352)
|
0.242
|
LDH > 245 U/L
|
44 (61.1%)
|
47 (72.3%)
|
0.206
|
Troponin↑ (No. (%))
|
7(13.7%)
|
12(21.4%)
|
0.298
|
NT-proBNP, pg/mL
|
159(67–411)
|
157(63–470)
|
0.832
|
NT-proBNP↑ (No. (%))
|
29(50.9%)
|
35(60.3%)
|
0.307
|
CRP, mg/L
|
220(4.2–50.8)
|
34.7(8.6–76.5)
|
0.153
|
CRP↑ (No. (%))
|
57(93.4%)
|
47(95.9%)
|
0.690
|
IL-6, pg/mL
|
12.3(5.2–25.5)
|
11.7(4.2–26.6)
|
0.672
|
IL-6↑ (No. (%))
|
26(59.5%)
|
15(42.9%)
|
0.145
|
Ferritin, µg/L
|
522.1(320.5–729.0)
|
729.5(367.8-1542.9)
|
0.055*
|
Ferritin↑ (No. (%))
|
39(90.7%)
|
34(97.1%)
|
0.372
|
PT, s
|
13.7(13.2–14.3)
|
13.8(13.4–14.2)
|
0.976
|
APTT, s
|
39.6(35.7–42.0)
|
39.5(37.7–45.9)
|
0.024*
|
APTT↑ (No. (%))
|
17(23.6%)
|
28(43.8%)
|
0.013*
|
FIB, g/L
|
4.86(3.85–6.05)
|
5.31(4.26–6.19)
|
0.237
|
D-Dimer, µg/mL
|
0.71(0.48–1.76)
|
1.17(0.51–2.07)
|
0.196
|
D-Dimer↑ (No. (%))
|
53(72.6%)
|
45(70.3%)
|
0.767
|
Clinical features, laboratory indices and treatment of severe COVID-19 hospitalized patients.
The characteristics of the current episode were collected, including fever (≥ 38 °C), chill, cough, chest pain, dyspnea, diarrhea and fatigue or myalgia. Each of the above symptoms were showed with different proportion of manifestations. Wheeze was the clinical feature of COVID-19 patients with influenza IgM-positive (26.4% vs 9.0%, P = 0.008). On contrary, fatigue or myalgia was the feature of the COVID-19 patients with IgM-negative and showed significant difference between groups (38.4% vs 58.2%, P = 0.019). In laboratory examination, increased levels of ferritin and prolonging APTT were showed in COVID-19 patients with influenza IgM-negative compared with patients in the other group with significant differences. According to the score of CURB-65, the severity of COVID-19 patients were evaluated and the proportion of mild grade in COVID-19 patients with influenza IgM positive group was much higher than the other group. Considering severity of the medical status, majority of the patients were under oxygen therapy, including nasal cannula, oxygen mask, NMV or HFNC and MV or ECMO, and other supportive treatment. Compound Methoxamine capsule were used for relieving the wheezing symptoms (Table 2).
Outcomes and related risk factors
The duration of viral shedding and the length of hospital stay were without differences between-groups. Death rate in the group of COVID-19 patients with influenza IgM-positive is lower than it in other group with significant differences (4.1%vs 14.9%, P = 0.040). The rest patients are matched the discharge criteria and fully recover within 28 days of observation period.
Univariate Regression analysis showed that several factors were associated with higher risk of death, which included increasing level of LDH, troponin, NT-proBNP and D-dimer, prolonging of PT and APTT, decreasing level of lymphocytes, platelet and eGFR. However, influenza virus IgM positive was associated with lower risk of death (Table 3).
Table 2
Treatment and prognosis of COVID-19 Patients with and Without Influenza IgM positive.
Study Population
|
With Influenza
IgM positive
No. (%) (n = 73)
|
Without Influenza
IgM positive
No. (%) (n = 67)
|
P value
|
Treatment in hospital
|
|
|
|
Oxygen Therapy
|
|
|
0.485
|
Nasal Cannula
|
30(41.1%)
|
27(40.3%)
|
|
Oxygen Mask
|
1(1.4%)
|
2(3.0%)
|
|
NMV + High-flow nasal cannula
|
39(53.4%)
|
35(52.2%)
|
|
IMV
|
1(1.4%)
|
3(4.5%)
|
|
ECMO
|
2(2.7%)
|
0
|
|
Drugs
|
|
|
|
Oseltamivir
|
33(45.2%)
|
23(34.3%)
|
0.189
|
Arbidol
|
53(72.6%)
|
47(70.1%)
|
0.748
|
Compound Methoxamine capsule
|
19(23.3%)
|
6(9.0%)
|
0.022*
|
Clinical outcomes
|
|
|
|
CURB-65
|
|
|
0.040*
|
Low risk
|
65(89.0%)
|
50(74.6%)
|
|
Medium risk
|
6(8.2%)
|
8(11.9%)
|
|
High risk
|
2(2.7%)
|
9(13.4%)
|
|
Duration of viral shedding, days
|
26(20–32)
|
25(21,32)
|
0.969
|
Hospital length of stay, days
|
13(11–18)
|
14(12,19)
|
0.411
|
Time from illness onset to discharge, days
|
28(22–35)
|
27(23–33)
|
0.867
|
Death (No. (%))
|
3(4.1%)
|
10(14.9%)
|
0.040*
|
Discharge (No. (%))
|
70(95.9%)
|
57(85.1%)
|
Table 3
Univariable Regression of Factors Associated with Death
|
Death
|
Patient characteristics and findings
|
OR, 95%CI
|
P value
|
Influenza
|
0.244(0.064,0.930)
|
0.039
|
LDH, U/L
|
1.006(1.003,1.010)
|
0.001
|
Troponin↑
|
18.90(4.91,72.76)
|
0.000
|
NT-proBNP↑
|
10.377(1.292,83.337)
|
0.028
|
PT, s
|
1.755(1.169,2.637)
|
0.007
|
APTT↑
|
3.719(1.141,12.126)
|
0.029
|
D-Dimer, µg/mL
|
1.180(1.029,1.354)
|
0.018
|
Lymphocytes < 0.8 × 109/mL
|
8.25(2.238,28.862)
|
0.001
|
PLT < 100 × 109/ mL
|
7.556 (1.858,30.730)
|
0.005
|
eGFR < 60 ml/min/1.73 m2
|
3.829(1.033,14.196)
|
0.045
|