Results
The median age of the 10 patients (6 men and 4 women) with COVID-19 was 44.95 years (range, 29–79 years). Of the 10 patients, 4 had hypertension, 2 were taking antihypertensive medications, 1 was receiving an angiotensin-converting enzyme inhibitor, and 1 was receiving an angiotensin II receptor blocker. On the basis of their supplemental oxygen use, the patients were divided into the mild and severe groups. Of the 4 patients in the severe group, 2 were intubated and were on mechanical ventilators, including 1 patient supported with a high-flow nasal cannula  via nasal prongs and 1 with nasal prongs only. Four patients in the severe group received lopinavir/ritonavir. In the mild group, 1 elderly patient with pneumonia received lopinavir/ritonavir and 1 with consistently low Ct values received hydroxychloroquine. The remaining patients in the mild group did not receive antiviral medications (Table 1).
Among the patients with COVID-19 observed in this study, the Ct values of the upper respiratory tract specimens were low during the early stages after symptom onset but gradually increased over time in both the severe and mild groups. Moreover, patients in the severe group had lower Ct values than those in the mild group did. The Ct values of theRdRP and E genes on day 6 after symptom onset were significantly lower in the severe group than in the mild group (p < 0.05). The values increased at a slower rate in the severe group than those in the mild group did during the first 3–6 days after symptom onset. Moreover, virus shedding lasted longer in the severe group (Figure 1).
The viral load in the lower respiratory tract specimens remained undetectable in the mild group 7 days after symptom onset. However, virus shedding persisted for more than 3 weeks in the severe group (Figure 2; see Appendix Figure 1 and Appendix Figure 2).
The positive rate of the SARS-CoV-2 on the PCR test—performed with a nasopharyngeal swab targeting theRdRP gene during the admission period—was 48.3% when the cut-off value was 35 and 74.1% when the cut-off value was 38. When theE gene was targeted, the positive rate of the SARS-CoV-2 on the PCR test performed with the nasopharyngeal swab was confirmed to be 55.2% when the cut-off value was 35 and 74.1% when the cut-off value was 38. The positive rate of the SARS-CoV-2 on the PCR test—performed with a sputum specimen targeting the RdRP gene—was 43.2% when the cut-off value was 35 and 50.0% when the cut-off value was 38. When the E gene was targeted, the positive rate of the SARS-CoV-2 on the PCR test performed with the sputum specimen was confirmed to be 46.3% when the cut-off value was 35 and 50.0% when the cut-off value was 38.
During hospitalization, Ct values for both the mild and severe group tended to be lower at symptom onset and tended to increase with time. In particular, 3 of 6 patients showed positive results on PCR even before symptom onset, and 2 of them had the lowest Ct values.
Of the 3 patients, one had a Ct value of 16.19 (nasopharyngeal swab,E gene) 2 days before symptom onset and the other had a Ct value of 13.75 (sputum specimen, E gene) 1 day before symptom onset. The Ct value of the test results during the asymptomatic phase of these 3 patients (patient E, patient G, and patient J) was included in the result of day 0 after symptom onset, as shown in Figure 3.
The mean ± standard error of the mean (SEM) Ct value obtained using the nasopharyngeal swab during the incubation period was 22.20 ± 4.0 when the RdRP gene was targeted and 21.28 ± 3.88 when the Egene was targeted. The mean Ct value obtained using the sputum specimen was 22.46 ± 6.02 when the RdRP gene was targeted and 23.33 ± 7.18 when the E gene was targeted during the incubation period. The lowest Ct value was observed on day 3 after symptom onset, and the mean Ct value obtained using the nasopharyngeal swab was 21.49 ± 1.91 when the RdRP gene was targeted and 21.19 ± 1.94 when the Egene was targeted. The mean Ct value obtained using the sputum specimen was 19.76 ± 1.61 when the RdRP gene was targeted and 18.88 ± 1.01 when the E gene was targeted (Figure 3; Table 2).
The chest radiograph scores were higher in the severe group than in the mild group and were significantly different on days 9, 12, and 15 after the onset of symptoms. Moreover, the chest radiograph scores in the severe group were the highest at approximately 3 weeks after symptom onset (Figure 4; see Appendix Figure 3).