Baseline characteristics
A total of 140 adult patients confirmed with COVID-19 from designated hospital was enrolled in this study, with 73 patients (52.14%) were identified as influenza virus IgM-positive. 76 (54.4%) of the COVID-19 patients were males. The median age of patients with influenza virus-IgM negative was 66 years (IQR, 55 to 70 years), older than patients with influenza virus IgM-positive (median age 62, IQR, 47 to 70 years, P = 0.1118). Chronic comorbidities consisting mainly of hypertension (45.3%), diabetes (15.8%), chronic respiratory disease (7.2%), cardiovascular disease (5.8%), malignancy (4.3%) and chronic kidney disease (2.2%). Clinical features, including fever (≥38°C), chill, cough, chest pain, dyspnea, diarrhea and fatigue or myalgia were collected. Fatigue or myalgia was less found in COVID-19 patients with IgM-positive (33.3% vs 50/7%, P = 0.0375). (Table 1)
Table 1. Clinical Characteristics of COVID-19 Patients with and Without Influenza IgM positive.
Study Population
|
With Influenza IgM positive (n=73)
|
Without Influenza IgM positive (n=67)
|
Total (n=140)
|
P value
|
Demographic
|
|
|
|
|
Gender, Male
|
39 (53.4)
|
37 (55.2)
|
76 (54.3)
|
0.8310
|
Age, media (IQR), yrs
|
62.0 (47.0, 70.0)
|
66.0 (55.0, 70.0)
|
65.0 (48.5, 70.0)
|
0.1118
|
Comorbidities
|
|
|
|
|
Hypertension
|
32/70 (45.7)
|
30/67 (44.8)
|
62/137 (45.3)
|
0.9122
|
Diabetes
|
12/72 (16.7)
|
10/67 (14.9)
|
22/139 (15.8)
|
0.7787
|
Chronic respiratory disease
|
5/72 (6.9)
|
5/67 (7.5)
|
10/139 (7.2)
|
0.9060
|
Cardiovascular disease
|
5/72 (6.9)
|
3/67 (4.5)
|
8/139 (5.8)
|
0.5301
|
Malignancy
|
3/72 (4.2)
|
3/67 (4.5)
|
6/139 (4.3)
|
0.9282
|
Chronic kidney disease
|
2/72 (2.8)
|
1/67 (1.5)
|
3/139 (2.2)
|
0.5983
|
Signs and symptoms
|
|
|
|
|
Fever
|
55 (75.3)
|
53 (79.1)
|
108 (77.1)
|
0.5964
|
Highest temperature, °C
|
38.5 (38.0, 39.0)
|
38.7 (38.2, 39.0)
|
38.5 (38.0, 39.0)
|
0.1274
|
Chills
|
13 (17.8)
|
19 (28.4)
|
32 (22.9)
|
0.1375
|
Cough
|
41/72 (56.9)
|
44/67 (65.7)
|
85/139 (61.2)
|
0.2915
|
Productive cough
|
20/72 (27.8)
|
25/67 (37.3)
|
45/139 (32.4)
|
0.2299
|
Chest pain/Chest congestion
|
19/72 (26.4)
|
13/67 (19.4)
|
32/139 (23.0)
|
0.3283
|
Dyspnea
|
21/72 (29.2)
|
29/67 (43.3)
|
50/139 (36.0)
|
0.0831
|
Diarrhea
|
18 (24.7)
|
25 (37.3)
|
43 (30.7)
|
0.1049
|
Fatigue or myalgia
|
24/72 (33.3)
|
34/67 (50.7)
|
58/139 (41.7)
|
0.0375
|
Laboratory findings, median (IQR)
|
|
|
|
|
White blood cells, ×109/mL
|
5.7 (4.2, 6.8)
|
5.7 (4.6, 7.9)
|
5.7 (4.4, 7.2)
|
0.3226
|
Neutrophils, ×109/mL
|
3.9 (2.5, 4.8)
|
4.0 (2.6, 5.9)
|
3.9 (2.5, 5.3)
|
0.3600
|
Lymphocytes, ×109/mL
|
1.2 (0.9, 1.6)
|
1.1 (0.8, 1.5)
|
1.1 (0.8, 1.5)
|
0.3826
|
Lymphocytes<0.8×109/mL
|
18/73 (24.7)
|
18/66 (27.3)
|
36/139 (25.9)
|
0.7252
|
Red blood cells, ×1012/mL
|
4.1 (3.6, 4.6)
|
4.0 (3.7, 4.4)
|
4.0 (3.7, 4.5)
|
0.4502
|
Platelets, ×109/ mL
|
230.0 (173.0, 292.0)
|
253.0 (169.0, 340.0)
|
235.0 (169.0, 312.0)
|
0.3622
|
Platelets<100×109/mL
|
5/73 (6.8)
|
6/66 (9.1)
|
11/139 (7.9)
|
0.6249
|
Hemoglobin, g/L
|
122.0 (114.0, 137.0)
|
125.5 (113.0, 137.0)
|
123.0 (113.0, 137.0)
|
0.9143
|
ALT, U/L
|
23.0 (17.0, 40.0)
|
22.5 (15.0, 41.0)
|
23.0 (16.0, 41.0)
|
0.7373
|
AST, U/L
|
26.0 (19.0, 37.0)
|
30.0 (19.0, 41.0)
|
28.0 (19.0, 39.0)
|
0.3370
|
Albumin, g/L
|
36.1 (32.2, 38.3)
|
35.0 (31.4, 37.1)
|
35.2 (31.7, 38.1)
|
0.2945
|
Creatinine, μmol/L
|
70.0 (60.0, 89.5)
|
70.0 (59.0, 87.0)
|
70.0 (59.0, 89.0)
|
0.8596
|
LDH, U/L
|
268.5 (204.0, 329.5)
|
287.0 (235.0, 351.0)
|
281.0 (212.0, 334.0)
|
0.2419
|
LDH > 245 U/L
|
44/72 (61.1)
|
47/65 (72.3)
|
91/137 (66.4)
|
0.1658
|
Troponin>15.6pg/mL, No (%)
|
7/51 (13.7)
|
12/56 (21.4)
|
19/107 (17.8)
|
0.2977
|
NT-proBNP, pg/mL
|
140.0 (60.0, 334.0)
|
157.0 (64.0, 459.0)
|
151.0 (63.0, 411.0)
|
0.2883
|
NT-proBNP≥247pg/mL, No (%)
|
29/57 (50.9)
|
35/58 (60.3)
|
64/115 (55.7)
|
0.3069
|
CRP, mg/L
|
21.3 (4.1, 49.2)
|
34.7 (9.1, 73.4)
|
27.2 (6.1, 69.8)
|
0.1281
|
CRP≥1mg/L, No (%)
|
57/61 (93.4)
|
47/49 (95.9)
|
104/110 (94.5)
|
0.5651
|
IL-6, pg/mL
|
9.8 (4.2, 21.1)
|
6.8 (3.6, 23.2)
|
9.4 (3.9, 23.2)
|
0.5603
|
IL-6≥7pg/mL, No (%)
|
25/42 (59.5)
|
15/35 (42.9)
|
40/77 (51.9)
|
0.1450
|
Ferritin, μg/L
|
522.1 (320.5, 729.0)
|
630.5 (310.2, 1519.9)
|
562.6 (320.5, 986.5)
|
0.0964
|
Ferritin>150μg/L, No (%)
|
39/43 (90.7)
|
33/35 (94.3)
|
72/78 (92.3)
|
0.5495
|
PT, s
|
13.7 (13.2, 14.3)
|
13.8 (13.4, 14.2)
|
13.8 (13.3, 14.3)
|
0.9762
|
APTT, s
|
39.6 (35.8, 42.0)
|
39.5 (37.8, 45.8)
|
39.6 (36.6, 44.3)
|
0.0243
|
APTT>42s, No (%)
|
17/72 (23.6)
|
28/64 (43.8)
|
45/136 (33.1)
|
0.0127
|
FIB, g/L
|
4.9 (3.9, 6.0)
|
5.3 (4.3, 6.2)
|
5.0 (4.1, 6.1)
|
0.2374
|
D-Dimer, μg/mL
|
0.7 (0.5, 1.7)
|
1.2 (0.5, 2.1)
|
1.0 (0.5, 2.0)
|
0.2371
|
D-Dimer≥0.5μg/mL, No (%)
|
53/73 (72.6)
|
45/64 (70.3)
|
98/137 (71.5)
|
0.7669
|
Note. Data are presented as n (%) or median (IQR, interquartile range) for each parameter. P values were calculated by chi-square test, Fisher’s exact test, or Mann-Whitney U test, where appropriate.
Abbreviations. IQR, interquartile range; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactic Acid dehydrogenase; CRP, C-reactive protein; IL-6, interleukin-6; PT, prothrombintime; APTT, activated partial thromboplastin time; FIB, fibrinogen
Laboratory findings
Higher proportion of prolonged activated partial thromboplastin time (APTT) > 42 s was observed in COVID-19 patients with influenza virus IgM-negative (43.8% vs 23.6%, P = 0.0127). (Table1) Counts of lymphocytes and platelets were significantly lower, while aspartate aminotransferase (AST), creatinine, lactate dehydrogenase (LDH), troponin, NT-proBNP, C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, prothrombin time (PT), APTT and D-Dimer were significantly higher in dead cases (all P < 0.05). (Supplementary table 1)
Treatment and outcomes
43.6% of the patients received nasal cannula, 2.1% oxygen mask, 49.3% non-invasive mechanical ventilation (NMV)/high-flow nasal cannula (HFNC) and 8.6% invasive mechanical ventilation (IMV)/extracorporeal membrane oxygenation (ECMO). Compound Methoxamine capsule were used in more patients with influenza IgM positive than the other group (23.3% vs 9.0%, P = 0.0222). (Table 2) Higher levels of respiratory support were more seen in dead patients, especially those with influenza IgM positive. (Supplementary table 1 and Supplementary table 2)
According to the score of CURB-65, more COVID-19 patients with influenza IgM positive group were in low to moderate risk level (P = 0.0397). No differences were observed in the duration of viral shedding, the length of hospital stay and time from illness onset to discharge between groups. 9.3% of the patients died in hospital and the rate of death was significantly lower in patients with IgM positive than those with IgM negative (4.1% vs 14.9%, P = 0.0276). (Table 2)
Table 2. Treatment and prognosis of COVID-19 Patients with and Without Influenza IgM positive.
Study Population
|
With influenza IgM positive (n=73)
|
Without influenza IgM positive (n=67)
|
Total (n=140)
|
P value
|
Treatment in hospital
|
|
|
|
|
Oxygen Therapy
|
|
|
|
|
Nasal Cannula
|
32 (43.8)
|
29 (43.3)
|
61 (43.6)
|
0.9475
|
Oxygen Mask
|
1 (1.4)
|
2 (3.0)
|
3 (2.1)
|
0.5069
|
NMV/High-flow nasal cannula
|
35 (47.9)
|
34 (50.7)
|
69 (49.3)
|
0.7405
|
IMV/ECMO
|
7 (9.6)
|
5 (7.5)
|
12 (8.6)
|
0.6535
|
Drugs
|
|
|
|
|
Oseltamivir
|
33 (45.2)
|
23 (34.3)
|
56 (40.0)
|
0.1894
|
Arbidol
|
53 (72.6)
|
47 (70.1)
|
100 (71.4)
|
0.7482
|
Compound Methoxamine capsule
|
17 (23.3)
|
6 (9.0)
|
23 (16.4)
|
0.0222
|
Clinical outcomes
|
|
|
|
|
CURB-65
|
|
|
|
0.0397
|
Low risk
|
65 (89.0)
|
50 (74.6)
|
115 (82.1)
|
Medium risk
|
6 (8.2)
|
8 (11.9)
|
14 (10.0)
|
High risk
|
2 (2.7)
|
9 (13.4)
|
11 (7.9)
|
Duration of viral shedding, days
|
26.0 (20.0, 32.0)
|
25.0 (21.0, 32.0)
|
25.5 (20.5, 32.0)
|
0.9694
|
Hospital length of stay, days
|
13.0 (10.0, 18.0)
|
14.0 (10.0, 17.0)
|
13.0 (10.0, 18.0)
|
0.9084
|
Time from illness onset to discharge, days
|
27.0 (22.0, 35.0)
|
27.0 (21.0, 33.0)
|
27.0 (22.0, 33.5)
|
0.6208
|
Death ,No (%)
|
|
|
|
0.0276
|
Discharge
|
70 (95.9)
|
57 (85.1)
|
127 (90.7)
|
Death
|
3 (4.1)
|
10 (14.9)
|
13 (9.3)
|
Severe COVID-19 Patients with influenza virus IgM positive have a higher cumulative survivor rate than that of patients with influenza virus IgM negative (Log-rank P= 0.0308). Considering age is a potential confounding variable, difference in age was adjusted between different influenza virus IgM status groups, the HR was 0.29 (95% CI, 0.081-1.100). Similarly, difference in gender was adjusted as above, the HR was 0.262 (95% CI, 0.072-0.952) in the COX regression model. (Figure 2)