Shorter incubation period is associated with severe disease progression in patients with COVID-19

Figures & data

Table 1. Demographical characteristics of enrolled patients categorized by onset time

	Immediate onset (N = 57)	Late onset (N = 75)	P	Total (N = 330)
Age, years	52.0(32.0–60.5)	36.0(12.0–53.0)	<0.001	47.0(33.0–60.0)
Gender, female	35(61.4%)	39(52.0%)	0.281	169(52.2%)
Onset of exposure to symptom, days	2.0(1.0–3.0)	14.0(12.0–18.0)	<0.001	7.0(4.0–12.0)
Length of stay, days	16.0(14.0–20.0)	12.0(8.0–15.0)	<0.001	15.0(13.0–18.0)
Preexisting conditions
Any	10(17.5%)	9(12.0%)	0.369	77(23.3%)
Diabetes	2(3.5%)	1(1.3%)	0.393	18(5.5%)
Hypertension	5(8.8%)	6(8.0%)	0.874	38(11.5%)
Chronic liver disease	2(3.5%)	0	0.102	8(2.4%)
COPD	2(3.5%)	1(1.3%)	0.406	11(3.3%)
Heart disease	1(1.8%)	0	0.250	15(4.5%)
Cancer	1(1.8%)	1(1.3%)	0.844	3(0.9%)
Cerebrovascular disease	1(1.8%)	0	0.250	2(0.6%)
Coinfected with other virus	2(3.5%)	3(4.0%)	0.884	6(1.8%)
Clinical type on admission			<0.001
Mild	6(10.5%)	24(32.0%)		74(22.4%)
Common	47(82.5%)	48(64.0%)		227(68.8%)
Severe	4(7.0%)	3(4.0%)		25(7.6%)
Critical	0	0		4(1.2%)

Table 2. Clinical symptoms and laboratory tests of enrolled patients categorized by onset time

	Immediate onset (N = 57)	Late onset (N = 75)	P	Total (N = 330)
Body temperature, °C	37.0(36.6–37.5)	36.7(36.5–37.2)	0.125	37.0(36.6–37.5)
<37.3	38(66.7%)	57(76.0%)		212(64.2%)
37.3–38	16(28.1%)	10(13.3%)		86(26.1%)
38.1–39	3(5.3%)	8(10.7%)		31(9.4%)
≥39	0	0		1(0.3%)
Symptoms on admission
Fever	47(82.5%)	44(58.7%)	0.003	254(77.0%)
Cough	31(54.4%)	28(37.3%)	0.051	166(50.3%)
Sputum production	16(28.1%)	9(12.0%)	0.020	167(50.6%)
Shortness of breath	2(3.5%)	1(1.3%)	0.406	14(4.2%)
Fatigue	9(15.8%)	6(8.0%)	0.162	74(22.4%)
Loss of appetite	2(3.5%)	8(10.7%)	0.124	45(13.6%)
Nausea	0	2(2.7%)	0.214	10(3.0%)
Headache	6(10.5%)	2(2.7%)	0.061	27(8.2%)
Diarrhea	5(8.8%)	5(6.7%)	0.651	25(7.6%)
Sore throat	0	1(1.3%)	0.382	5(1.5%)
Nasal obstruction	0	1(1.3%)	0.382	2(0.6%)
Blood tests
WBC, ×109/L	4.36(3.11–5.57)	4.79(3.80–5.84)	0.032	4.60(3.58–5.72)
Neutrophils, ×109/L	2.59(1.64–3.69)	2.42(1.68–3.31)	0.883	2.58(1.89–3.48)
Lymphocytes, ×109/L	1.17(0.99–1.38)	1.56(1.12–2.29)	<0.001	1.27(0.98–1.73)
Platelets, ×109/L	166.0(138.5–208.5)	191.0(160.0–253.0)	0.007	180.0(143.0–224.0)
Hemoglobin, g/L	135.0(127.5–144.5)	137.0(123.0–145.0)	0.746	136.0(126.8–146.0)
T lymphocyte	744.0(481.0–1165.0)	1198.0(882.3–1621.0)	0.006	970.5(627.3–1319.0)
CD4 + T lymphocyte	446.0(244.5–634.0)	625.0(447.0–911.5)	0.003	519.0(344.3–714.8)
CD8 + T lymphocyte	326.0(187.0–511.0)	442.5(325.0–655.0)	0.002	347.5(207.5–506.5)
Blood chemistry
TBIL, umol/L	10.3(7.8–13.6)	9.2(6.7–14.6)	0.294	9.8(7.6–14.6)
ALT, U/L	20.0(12.5–27.5)	19.0(15.0–29.0)	0.883	20.0(15.0–31.0)
AST, U/L	24.0(19.5–30.5)	28.0(21.0–38.0)	0.073	27.0(21.0–36.5)
BUN, mmol/L	4.1(3.2–5.1)	3.8(3.1–4.7)	0.377	3.9(3.2–4.9)
Cr, umol/L	64.0(48.5–78.0)	54.0(42.0–71.6)	0.024	62.5(50.0–75.4)
LDH, U/L	197.0(157.0–307.0)	238.0(186.5–480.0)	0.011	233.0(176.0–400.0)
cTnI, ug/L	0.012(0.006–0.012)	0.012(0.007–0.012)	0.202	0.012(0.006–0.012)
Creatine kinase, U/L	78.0(51.5–123.0)	72.0(49.3–92.9)	0.628	71.0(51.0–103.0)
Coagulation function
PT, s	11.9(11.1–12.5)	11.8(11.3–12.6)	0.514	11.9(11.3–12.5)
D-mer, s	0.39(0.29–0.63)	0.31(0.25–0.54)	0.067	0.37(0.26–0.55)
Infection-related biomarkers
Procalcitonin, ng/mL	0.046(0.031–0.076)	0.031(0.021–0.050)	<0.001	0.042(0.026–0.065)
C reactive protein, mg/L	9.9(4.3–26.4)	5.3(1.9–20.6)	0.054	10.3(3.9–27.3)
IL6, pg/ml	8.59(5.08–17.25)	4.82(3.12–15.96)	0.069	10.91(4.16–19.57)

Table 3. CT characteristics of enrolled patients categorized by onset time

	Immediate onset (N = 48)	Late onset (N = 61)	P	Total (N = 296)
CT scores	5.0(2.0–9.0)	7.0(3.0–11.0)	0.198	6.0(2.0–11.0)
Number of lobes involved			0.637
0	5(10.4%)	4(6.6%)		25(8.4%)
1 lobe	7(14.6%)	6(9.8%)		31(10.5%)
2 lobes	8(16.7%)	8(13.1%)		46(15.5%)
3 lobes	9(18.8%)	9(14.8%)		50(16.9%)
4 lobes	7(14.6%)	16(26.2%)		44(14.9%)
5 lobes	12(25.0%)	18(29.5%)		84(28.4%)
Bilateral Involvement	39(81.3%)	54(88.5%)	0.287	236(79.7%)
Opacity distribution			0.461
Peripheral	34(70.8%)	47(77.0%)		203 (68.6%)
Central	14(29.2%)	14(23.0%)		93(31.4%)
Opacity patterns
Pure GGO	19(39.6%)	43(70.5%)	0.001	203(68.6%)
Consolidation	33(68.8%)	51(83.6%)	0.067	210(70.9%)
“Crazy-Paving” Pattern	17(35.4%)	17(27.9%)	0.398	101(34.1%)
Nodules	0	0	NA	1(0.3%)
Linear opacities	19(39.6%)	29(47.5%)	0.406	139(47.0%)
Lung cavitation	3(6.3%)	0	0.048	10(3.4%)
Other findings
Lymphadenopathy	0	0	NA	0
Pleural effusion	0	0	NA	0
Emphysema	2(4.2%)	0	0.108	2(0.7%)
Fibrosis	5(10.4%)	8(13.1%)	0.666	39(13.2%)

Table 4. Treatment and prognosis during hospitalization of enrolled patients categorized by onset time

	Immediate onset (N = 57)	Late onset (N = 75)	P	Total (N = 330)
Treatment
Anti-coronavirus treatment	57(100%)	75(100%)	1	330(100%)
Glucocorticoids	15(26.3%)	14(18.7%)	0.293	89(27.0%)
Antibiotic treatment	22(38.6%)	8(10.7%)	<0.001	98(29.7%)
Immunoglobulin	15(26.3%)	11(14.7%)	0.096	80(24.2%)
Regulating gut microbiome	30(52.6%)	40(53.3%)	0.936	179(54.2%)
Mechanical ventilation	4(7.0%)	3(4.0%)	0.443	39(11.8%)
ECMO	0	0	NA	0
CRRT	0	0	NA	2(0.6%)
Aggravation during hospitalization
From mild/common type to severe type	10(17.5%)	9(12.0%)	0.369	62(18.8%)
From severe type to critical type	1(1.8%)	0	0.250	13(3.9%)
Admission to ICU	2(3.5%)	1(1.3%)	0.406	22(6.7%)
Any	10(17.5%)	9(12.0%)	0.369	70(21.2%)

Figure 1. Change trend of CT scores. (a) the overall change of the two group (median with 95% confidence interval). (b) the individual change in I group (c). the individual change in L group. This figure represented different CT severity score of each CT scan during hospitalization. In (b) and (c), each line and dot represented a single patient’s CT score in consecutive times. As the figure showed, there were more patients in I group with an elevated severity scores than in I group during first two examinations, which means more patients exacerbated in CT scan in the beginning

Table 5. Prognostic factors for CT aggravation by COX analysis

Factors	Adjusted COX analysis			Model 1		Model 2		Model 3
	HR(95%CI)	P value	HR(95%CI)		P value	HR(95%CI)	P value	HR(95%CI)		P value
Onset of exposure to symptom	0.39(0.19–0.82)	0.012	0.40(0.19–0.84)		0.016	0.36(0.14–0.94)	0.037	0.36(0.14–0.93)	0.035
Clinical type	2.12(1.06–4.25)	0.035	1.42(0.73–2.75)		0.307	1.08(0.37–3.16)	0.894	1.12(0.37–3.39)	0.840
Glucocorticoids use	3.50(1.79–6.82)	<0.001	2.08(0.26–16.51)		0.489	2.07(0.23–18.57)	0.515	2.31(0.26–20.98)	0.456
Immunoglobulin use	3.72(1.89–7.31)	<0.001	1.58(0.20–12.52)		0.666	0.77(0.08–7.44)	0.824	0.72(0.07–7.10)	0.782
Lymphocytes	0.63(0.38–1.05)	0.075				0.82(0.39–1.71)	0.600	0.89(0.42–1.91)	0.770
C reactive protein	2.67(1.30–5.48)	0.007				1.34(0.51–3.55)	0.557	1.34(0.50–3.59)	0.555
IL6	3.21(1.21–8.54)	0.020				1.88(0.61–5.79)	0.269	1.86(0.62–5.59)	0.271
Fatigue	2.86(1.43–5.70)	0.003						1.79(0.71–4.55)	0.219
Headache	2.44(0.95–6.27)	0.064						1.05(0.23–4.78)	0.955

Model 1: Age, Gender, Onset of exposure to symptom, Clinical type, Glucocorticoids use, Immunoglobulin use

Model 2: Age, Gender, Onset of exposure to symptom, Clinical type, Glucocorticoids use, Immunoglobulin use, Lymphocytes, C reactive protein, IL6

Model 3: Age, Gender, Onset of exposure to symptom, Clinical type, Glucocorticoids use, Immunoglobulin use, Lymphocytes, C reactive protein, IL6, Fatigue, Headache

Figure 2. Incidence rate of aggravation for the two groups. (a) aggravation of symptoms (b) aggravation of CT presentation. There was no difference in symptom aggravation between the two groups (P = 0.553), but CT severity score elevated significantly in I group than in L group (P = 0.042)

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.