Airway droplet transmission is the most important route of COVID-19 transmission. In the case of long-term exposure to high-concentration aerosols, there is also the possibility of aerosol transmission (5). Therefore, by detecting the novel respiratory coronavirus, we can determine whether patients with COVID-19 can excrete novel coronavirus and whether they are infectious. In China, a positive nasopharyngeal swab nucleic acid test is an important indicator for the diagnosis of COVID-19. Two consecutive negative nasopharyngeal swab RT-PCR tests is one of the conditions for patients to meet the discharge standards.
As shown in Table 1, for the overall patient group, the median virus duration was 17 days (IQR 13–22); for no severe patients, it was 15 days (IQR 12–19), and for severe patients, it was 20 days (IQR 15.5–27). There was a significant difference between the two groups, suggesting that it took longer for the severe patients to clear the novel coronavirus from the body. Clinical classification was an important factor for virus duration.
As shown in Table 2 and Fig. 1, it took 6 weeks for the overall patient group to reach 100% virus clearance; it took 5 weeks for the no severe patients and 6 weeks for the severe patients. To minimize the transmission of pathogens from the respiratory tract, the transmission route was cut off. For no severe patients who are not admitted to the hospital, the time of home isolation should be more than 5 weeks. The discharge standards should include two consecutive negative RT-PCR results to ensure that patients no longer discharge 2019 coronavirus. Due to various reasons, such as a shortage of medical resources, if COVID-19 patients are discharged without two consecutive negative RT-PCR results, we recommend that no severe patients continue to be home-isolated after discharge. The time from onset to the end of home isolation should be more than 5 weeks for no severe patients and more than 6 weeks for severe patients. Our view is similar to that of some epidemiologists(6)..
To clarify the factors influencing virus clearance, we performed a univariate analysis and multiple linear regression analysis on the baseline characteristics and treatment schemes in the overall patient group. As shown in Table 3 and 4, the factors influencing virus clearance within 2 weeks were treatment timing and glucocorticoid usage. The factors influencing virus clearance within 4 weeks were treatment timing, glucocorticoid usage and age.
This study showed that earlier treatment was a favorable factor for virus clearance. For patients with COVID-19, treatment should be started as soon as possible. Even if the patient's symptoms are mild or asymptomatic, early treatment is also meaningful. Because active treatment strategies are conducive to virus clearance, early treatment means successful management of the source of infection and fewer new infections. Similarly, for people with a history of exposure, rigorous monitoring is necessary, and early detection and initiation of treatment are conducive to the control of the epidemic. An article reported that COVID-19 can be treated as soon as possible to obtain a better clinical prognosis(7), and faster virus clearance may be the reason.
Our study showed that age was an important influencing factor of virus clearance. In all patients, age > 60 years was an unfavorable factor for virus clearance. This may be related to the decline of cellular and humoral immune functions in elderly people. Multiple studies have reported that the prognosis of COVID-19 was worse in elderly patients(8, 9), which may be related to the poor virus clearance of these patients. An article also reported that RNA virus detection testing in children's fecal samples took more time to turn negative than in adult samples(10), but our results showed no difference in virus clearance between patients aged < 18 years and 18–60 years. Since there were few patients aged < 18 years included in our study, the small sample size may be the reason.
Glucocorticoid usage can reduce inflammatory factors and chemokines, thereby reducing the excessive inflammatory response and reducing lung tissue damage, which is why glucocorticoids are often used in acute lung injury and ARDS(11). However, glucocorticoid usage in coronavirus pneumonia is controversial. Studies have supported the use of low to moderate doses of glucocorticoids in patients with coronavirus infection. A retrospective study(12) of 401 patients suggested that the correct use of glucocorticoids can reduce SARS mortality and shorten hospital stays. Recently, an article retrospectively analyzed a variety of viral infectious diseases, such as SARS, MERS, influenza, and respiratory syncytial virus infection, and found that the use of glucocorticoids had no significantly benefit. Therefore, the use of glucocorticoids in patients with COVID-19 is not recommended(13). A study also showed that glucocorticoid usage may lead to longer virus duration in COVID-19 patients (14). Our results show that glucocorticoid usage may be an adverse factor in viral clearance. From the perspective of virus clearance, glucocorticoid usage in new coronavirus pneumonia is not supported. However, viral clearance does not represent an improvement in clinical symptoms or lung function. The effects of glucocorticoids on clinical outcomes such as symptom improvement, length of hospital stay, and mortality should be further studied to assess the pros and cons of using glucocorticoids as a whole.
The antiviral drugs used in this study were lopinavir/ritonavir, ribavirin, arborol and different combinations of them. There were different kinds of antiviral schemes used in this study, but there were few patients in any specific scheme, so the impact of different antiviral schemes on virus clearance was difficult to assess. Therefore, we only compared the group using more than two antiviral drugs with the group using a single drug. Studies have shown that the combination of antiviral drugs has no stronger effect on virus clearance. The comparison of antiviral therapy and combined antiviral effects needs to be revealed by large, prospective controlled studies. The other clinical characteristics, including sex, underlying disease, BMI, smoking history, clinical symptoms, white blood cells, lymphocytes, common inflammatory factors, pneumonia severity, and antibiotics, according to this study, were not influencing factors for virus clearance.
Our research has some limitations. First, the detection of virus RNA in this study was only a qualitative test, not a quantitative test, so our study failed to analyze the changing process of viral load and its influencing factors. Second, our study only discussed the effect of glucocorticoids usage on virus clearance. Due to the small sample size, it was not possible to discuss whether the type, duration, daily dose, and total amount of glucocorticoids can affect virus clearance. There may be a method of using glucocorticoids that does not delay the virus clearance, but also helps control inflammation in the lungs.