Xia Yu and Shanshan Sun contributed equally to this work.
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The pandemic of coronavirus diseases 2019 (COVID-19) imposes a heavy burden on medical resources [1]. Whether there is correlation between viral load and disease severity has not been clarified. In the study, we retrospectively collected the virological data, as well as demographic, epidemiological clinical information of 92 patients with confirmed COVID-19 in a single hospital in Zhejiang Province, China. We compared the baseline viral loads between severe patients and those mild to moderate at admission and also between those developing severe disease during hospitalization and those not.
We studied 92 patients with confirmed COVID-19 who were admitted from January 19, 2020, to March 19, 2020, in the First Affiliated Hospital of Zhejiang University. The sputum specimens were collected from the lower respiratory tract of each patient at admission and the levels of viral nuclei acid were determined by a real-time PCR (RT-PCR) approach and indicated by the cycle threshold (Ct) values of RT-PCR assays [2]. Other demographic, epidemiological and clinical information were collected and inputted into a pre-designated electronic data collection form. All patients followed up to March 15, 2020. All the statistical analyses were performed using GraphPad Prism 5 (GraphPad Software Inc.; San Diego, CA, USA) and SPSS 20.0 (SPSS Inc.; Chicago, IL, USA).
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Of the 92 patients, 30 were severe on admission. Of the other 62 mild-moderate cases at admission, 11 cases became severe during hospitalization. The demographic, epidemiological and clinical information was shown in Table 1. All patients were tested for SARS-CoV-2 nucleic acid on sputum specimens from the lower respiratory tract at admission. As shown in Fig. 1a, severe patients had significantly lower Ct values than mild-moderate cases at admission (25 vs. 28, p = 0.017), suggesting a higher viral load in the lower respiratory tract. Furthermore, a higher viral load was observed in sputum specimens from patients who became severe during the hospitalization than those did not (24 vs. 29, p = 0.008). As shown in Fig. 1b, the Ct values of RT-PCR assays negatively correlated with the probability of progression to severe type in all the patients representing mild-to-moderate at admission.
Table 1
Demographic, comorbidities, epidemiological characteristics, and clinical and laboratory findings of patients with confirmed COVID-19 at admission
Variables
Total (n = 92)
Mild-moderate at admission
Severe at admission (n = 30)
P value*
Persistent mild-moderate during hospitalization (n = 51)
Mild-moderate to severe during hospitalization (n = 11)
P value#
Total (n = 62)
Demographic data
Age (years)
55 ± 16
49 ± 13
59 ± 17
0.032
51 ± 15
63 ± 16
0.001
Sex
Male
57 (62%)
26 (51%)
8 (72.7%)
34 (54.8%)
23 (76.7%)
Female
35 (38%)
25 (49%)
3 (27.3%)
0.189
28 (45.2%)
7 (23.3%)
0.043
Occupation
Agricultural worker
45 (48.9%)
25 (49%)
7 (63.6%)
32 (51.6%)
13 (43.3%)
Self-employed
21 (22.8%)
15 (29.4%)
2 (18.7%)
17 (27.4%)
4 (13.3%)
Employee
8 (8.7%)
5 (9.8%)
0 (0%)
5 (8.1%)
3 (10%)
Retired
17 (18.5%)
5 (9.8%)
2 (18.2%)
7 (11.3%)
10 (33.3%)
Students
1 (1.1%)
1 (2%)
0 (0%)
0.669
1 (1.6%)
0 (0%)
0.082
Smoking history
Yes
16 (17.4%)
7 (13.7%)
3 (27.3%)
17 (27.4%)
6 (20%)
No
76 (82.6%)
44 (86.3%)
8 (72.7%)
0.268
45 (72.6%)
24 (80%)
0.441
Comorbidities
Hypertension
33 (35.9%)
10 (19.6%)
7 (63.6%)
0.003
17 (27.4%)
16 (53.3%)
0.016
Diabetes
9 (9.8%)
1 (2%)
2 (18.2%)
0.024
3 (4.8%)
6 (20%)
0.022
Cardiovascular disease
8 (8.7%)
2 (3.9%)
1 (9.1%)
0.472
3 (4.8%)
5 (16.7%)
0.060
Chronic liver diseases
4 (4.3%)
2 (3.9%)
1 (9.1%)
0.472
3 (4.8%)
1 (3.3%)
0.741
Chronic renal diseases
3 (3.3%)
0 (0%)
1 (9.1%)
0.031
1 (1.6%)
2 (6.7%)
0.203
Others
6 (6.5%)
0 (0%)
2 (18.2%)
0.002
2 (3.2%)
4 (13.3%)
0.067
Epidemiological characteristics
Exposure to confirmed cases
46 (50%)
30 (58.8%)
5 (45.5%)
0.421
35 (56.5%)
11 (36.7%)
0.077
Family cluster
27 (29.3%)
15 (29.4%)
4 (36.4%)
0.653
19 (30.6%)
8 (26.7%)
0.696
Recent travel or residence to/in epidemic area
25 (27.2%)
11 (21.6%)
4 (36.4%)
0.303
15 (24.2%)
10 (33.3%)
0.358
Signs and symptoms
Fever
84 (91.3%)
45 (88.2%)
11 (100%)
0.235
56 (90.3%)
28 (93.3%)
0.633
Cough
58 (63%)
32 (62.7%)
7 (63.6%)
0.956
39 (62.9%)
13 (43.3%)
0.968
Fatigue
6 (6.5%)
1 (2%)
2 (18.2%)
0.024
3 (4.8%)
3 (10%)
0.350
Diarrhea
7 (7.6%)
1 (2%)
1 (9.1%)
0.229
2 (3.2%)
5 (16.7%)
0.023
Nausea and vomiting
4 (4.3%)
3 (5.9%)
1 (9.1%)
0.697
4 (6.5%)
0 (0%)
0.157
Shortness of breath
25 (27.2%)
2 (3.9%)
4 (36.4%)
0.001
6 (9.7%)
19 (63.3%)
< 0.001
Time to admission
3 (4)
4 (3)
1 (4)
0.011
4 (4)
1 (4)
0.211
Time to confirmed diagnosis
5 (5)
5 (4)
4 (4)
0.160
5 (4)
3 (6)
0.239
Laboratory parameters
WBC
6.5 (5.9)
5.2 (4.1)
7.5 ± 3.4
0.188
5.4 (4.5)
10.8 ± 5.6
< 0.001
Lymphocyte
0.8 (0.6)
0.97 ± 0.47
0.7 (0.4)
0.147
0.9 (0.7)
0.5 (0.5)
0.001
Platelet
191 (76)
193 (83)
170 ± 56
0.159
192 (84)
191 ± 45
0.851
CRP
27 (37)
13 (27)
37 ± 27
0.036
16 (30)
39 (29)
< 0.001
ALT
23 (22)
23 (24)
17 (15)
0.338
22 (23)
23 (16)
0.723
AST
22 (16)
21 (12)
21 (18)
1.000
21 (12)
26 (23)
0.236
Cr
75 (25)
71 ± 26
84 (39)
0.054
73 (28)
84 (33)
0.019
INR
0.98 (0.09)
0.97 ± 0.08
0.97 (0.04)
0.507
0.97 ± 0.06
1.01 ± 0.09
0.050
Bilirubin
10.8 (6.0)
12.2 (5.0)
10.0 (6.0)
0.912
10.6 (5.0)
12.6 (9.0)
0.097
LDH
281 ± 105
227 (103)
279 ± 101
0.376
229 (113)
339 (121)
< 0.001
CK
70 (76)
63 (61)
76 (60)
0.495
64 (58)
97 (172)
0.011
Urea nitrogen
5.3 (3.7)
4.4 (1.7)
6.8 (6.9)
< 0.001
4.6 (2.2)
7.7 (4.2)
< 0.001
CT scan
Normal
3 (3.3%)
3 (5.9%)
0 (0%)
3 (4.8%)
0 (0%)
Local lesion
5 (5.4%)
4 (7.8%)
0 (0%)
4 (6.5%)
1 (3.3%)
Multi-lesions
84 (91.3%)
44 (86.3%)
11 (100%)
1.000
55 (88.7%)
29 (96.7%)
1.000
ICU admission
27 (29.3%)
0 (0%)
8 (72.7%)
< 0.001
8 (12.9%)
19 (63.3%)
< 0.001
Data are expressed as number (percent), mean ± standard deviation (SD), or median (IQR)
#P values comparing data between patients becoming severe and those who did not during hospitalization by the Mann-Whitney U test, chi-squared test, or Fisher’s exact test
*P values comparing data between mild-moderate patients and severe patients at admission
Fig. 1
a Comparison of baseline sputum viral load between severe and mild-to-moderate patients at admission or between those becoming severe and those did not during the hospitalization. b Relationship between the estimated probability of disease progression during the hospitalization and baseline sputum viral load. Viral load is indicated by the Ct value of RT-PCR assay. The asterisk indicates a P value < 0.05
×
We found that the viral load of the sputum specimen in the lower respiratory tract tested at baseline is closely related to the severity of COVID-19. More importantly, patients with a higher baseline viral load are more likely to become severe. This finding apparently justifies the concept that early antiviral treatment, if effective, would reduce the risk of progression and thereby the mortality, which has been demonstrated in influenza [3]. In our study, sputum specimens were used, instead of nasopharyngeal and oropharyngeal swabs because it has been shown that samples from lower respiratory tract generally contain a higher level of viral load than nasopharyngeal and oropharyngeal swabs [4] and acquiring swabs is uncomfortable for patients.
In summary, we found a positive association between sputum viral load and disease severity as well as risk of progression.
Acknowledgements
Not applicable.
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Ethics approval and consent to participate
This study is reviewed and approved by the ethics committee of the First Affiliated Hospital of Zhejiang University. Following a full explanation of the study, written consent was obtained from each patient or his/her authorized representatives.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
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