Delayed Clearance of Viral RNA in Sputum for Severity COVID-19 Patients with Initial High Viral Load

Figures & data

Table 1 Demographic and Clinical Characteristics of COVID-19 Patients in Different Disease Severity Groups

Variables	Mild Group (N = 30)	Severe or Critical Group (N = 74)	p-value
Demographics
Age (years)	47.07 ± 13.87	55.58 ± 15.98	0.013
Sex (male%)	13 (12.5%)	51 (49.0%)	0.015
BMI (kg/m^2)	23.74 ± 3.36	24.43 ± 3.61	0.375
Comorbidities
Hypertension	4 (3.8%)	33 (31.7%)	0.003
Diabetes	3 (2.9%)	8 (7.7%)	0.903
Coronary heart disease	3 (2.9%)	3 (2.9%)	0.475
Liver diseases^♀	3 (2.9%)	14 17.3%)	0.210
Symptoms
Fever	22 (21.2%)	61 (51.7%)	0.295
Cough	18 (17.3%)	43 (41.3%)	0.859
Expectoration	11 (10.6%)	18 (17.3%)	0.203
Tachypnea	2 (6.7%)	20 (19.2%)	0.021
Dyspnea^&	0	13 (13.7%)	0.025
Experience tests
Leukocyte count (10^9 /L)	5.43 ± 3.59	8.24 ± 5.01	0.002
Lymphocyte (10^9 /L)	1.06 ± 0.45	0.77 ± 0.43	0.003
Virus CT values	29.55 ± 6.03	26.07 ± 5.43	0.009
Antivirals
Arbidol	27 (26.0%)	68 (65.4%)	0.759
Lopinavir/ritonavir	25 (24.0%)	55 (52.9%)	0.323
Darunavir/cobicistat	11 (10.9%)	28 (27.7%)	0.929
Favipiravir	4 (4.3%)	14 (14.9%)	0.498
Duration of fever (days)	5 (2–8)	7 (4–10)	0.013
Duration of viral RNA positive in sputum (days)	7 (5–14)	12 (8–20)	0.003
Time to radiological improvement (days)	9 (5–13)	10 (7–13)	0.190

Notes: ^♀liver disease, including chronic hepatitis B and non-alcoholic fatty liver disease and: oxygen saturation < 93%. Data are expressed as the mean ± standard deviation, median (Q1–Q3) or number (percent). Comparisons between groups were performed using one-way ANOVA, the Mann–Whitney U-test, or a chi-squared test.

Abbreviations: BMI, body mass index; CHD, coronary heart disease; CT values, cycle threshold values of RT-PCR; Diabetes, diabetes mellitus requiring treatment.

Table 2 Characteristics of Patients with or without Delayed Clearance of SARS-CoV-2 in COVID-19 Patients

Variables	With Delayed Clearance (N = 48)	Without Delayed Clearance (N = 56)	p-value
Demographics
Age (years)	56.80 ± 17.46	49.83 ± 13.64	0.028
Sex (male%)	35 (72.9%)	29 (51.8%)	0.027
BMI (kg/m^2)	23.74 ± 3.36	24.43 ± 3.61	0.375
Comorbidities
Hypertension	18 (37.5%)	19 (33.9%)	0.704
Diabetes	5 (10.4%)	6 (10.7%)	0.961
Coronary heart disease	4 (2.98.3%)	2 (3.6%)	0.297
Liver diseases^♀	8 (18.8%)	9 (16.1%)	0.719
Disease severity			< 0.001
Mild	9 (18.8%)	21 (37.5%)
Severe	26 (54.2%)	21 (60.7%)
Critical	13 (27.1%)	1 (1.8%)
Treatments hospitalization
Arbidol	46 (95.8%)	49 (87.5%)	0.132
Lopinavir/ritonavir	34 (70.8%)	46 (82.1%)	0.172
Darunavir/cobicistat	25 (13.9%)	14 (25.5%)	0.003
Favipiravir	13 (30.2%)	5 (9.8%)	0.012
Used glucocorticoid	40 (97.6%)	41 (97.6%)	0.986
Used immunoglobulin	29 (60.4%)	21 (37.5%)	0.020
Used glycyrrhizin acid^&	12 (25.0%)	16 (28.6%)	0.682
Duration of temperature fever (days)	8 (6–13)	5 (2–7)	< 0.001
Time to radiological improvement (days)	13 (9–16)	8 (5–12)	< 0.001

Notes: ^♀Liver disease, including chronic hepatitis B and non-alcoholic fatty liver disease. ^&Including compound glycyrrhizin acid diamine and compound glycyrrhizin monoamine. Data are expressed as the mean ± standard deviation, median (Q1–Q3) or number (percent). Comparisons between groups were performed using one-way ANOVA, the Mann–Whitney U-test, or a chi-squared test. Diabetes: diabetes mellitus requiring treatment. IVIG: intravenous immunoglobulin.

Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CHD, coronary heart disease; CRP, C-reactive protein; CT values, cycle threshold values of RT-PCR; Diabetes, diabetes mellitus requiring treatment; GGT, γ-glutamyltransferase; HBV, hepatitis B virus; INR, international normalized ratio; LDH, lactate dehydrogenase; PCT, procalcitonin;

Figure 1 Comparison of experience tests in COVID-19 patients with or without delayed clearance of SARS-CoV-2 during hospitalization. (A) The leukocyte count increased significantly (p = 0.011) in the group with delayed virus clearance. (B) The neutrophil count increased significantly (p = 0.032) in the group with delayed virus clearance. (C) The lymphocyte decreased significantly (p = 0.001) in the group with delayed virus clearance. (D) The virus CT values decreased significantly (p = 0.030) in the group with delayed virus clearance. (E) The levels of creatinine increased significantly (p = 0.030) in the group with delayed virus clearance. (F) The difference between the two groups were not significant (p = 0.141) in serum bilirubin.

Table 3 Susceptibility Risk Factors Associated with Delayed Clearance of SARS-CoV-2 in Sputum

Variables	Univariate Analysis		Multivariate Analysis
	OR (95% CI)	p-value	OR (95% CI)	p-value
Age (years)	1.03 (1.003–1.06)	0.032	-	-
Sex (male)	2.51 (1.10–5.72)	0.029	-	-
Classification of COVID-19	3.42 (1.66–7.04)	0.001
Mild	0.39 (0.16–0.95)	0.038	-	-
Critical	20.43 (2.56–163.13)	0.004	-	-
Experience tests
Leukocyte count (10^9 /L)	1.14 (1.03–1.25)	0.008
Lymphocyte (10^9 /L)	0.27 (0.10–0.73)	0.010	-	-
Creatinine (μmol/L)	1.02 (0.999–1.04)	0.062	-	-
Virus CT values	0.86 (0.79–0.94)	0.001	-	-
Treatments during hospitalization
Darunavir/cobicistat	3.49 (1.51–8.07)	0.004	4.25 (1.25–14.42)	0.020
Favipiravir	3.99 (1.29–12.33)	0.016	-	-
Immunoglobulin	2.54 (1.52–5.61)	0.021
Duration of temperature fever (days)	1.20 (1.08–1.33)	0.001	1.15 (1.03–1.30)	0.015
Time to radiological improvement (days)	1.22 (1.10–1.35)	< 0.001	1.14 (1.01–1.30)	0.033

Notes: Statistical analysis was performed using univariate analysis and multivariable logistic regression analysis. For delayed clearance of SARS-CoV-2 in sputum, the variables entered into the multivariate analysis were years, sex, critical COVID-19, leukocyte count, lymphocytopenia, virus CT value, treatment with darunavir/cobicistat, treatment with favipiravir, treatment with IVIG, duration of fever and time for radiological improvement.

Abbreviations: CI, confidence interval; COVID-19, coronavirus disease 2019. IVIG, intravenous immunoglobulin; OR, odds ratio; Virus CT values, the cycle threshold values of RT-PCR assays.

Figure 2 Used univariate analysis and multivariate analysis for susceptibility factors associated with delayed clearance of SARS-CoV-2 during hospitalization. (A) Univariate analysis for susceptibility factors associated with delayed clearance of SARS-CoV-2 during hospitalization; (B) multivariate analysis for susceptibility factors associated with delayed clearance of SARS-CoV-2 during hospitalization.