Globally, as of March 18, 2022, more than 420 million confirmed cases of COVID-19 and nearly 6 million deaths have been reported by the World Health Organization. After experiencing several pandemic waves caused by wild-type, Alpha, Delta, and Omicron variants of concerns, novel recombination DeltaCron has just been reported, alarming that the pandemic is “not over.” The Omicron variant continues to dominate the world, but its infection causes significantly less severe cases because of the global vaccination program. Leaving medical resources for the most vulnerable individuals should be the top priority. Preparing affordable medical facilities is the key to saving more lives in the face of a pandemic.
The “dynamic clearing” policy for SARS-CoV-2 control and prevention in China has successfully contained viral spread. Under this policy, all imported SARS-CoV-2–infected individuals were admitted to a government-designated hospital for treatment. When viral RNA is consecutively negative at least twice more than a 24 hours apart, they are discharged and subjected to another 14-day isolated observation in hotels or hospitals before finally returning to normal life. Such measures, relying on a profound economic basis, have substantially prevented the virus from re-entering the country from imported cases.
2. Research presentation
This study was approved by Guangzhou Eighth People’s Hospital Ethics Committee (nos. 202001134 and 202115202). Two thousand two hundred twelve imported cases in Guangzhou from January to December 2021 retrospectively analyzed. All patients were required to receive the first in-hospital treatment period and were subjected to a subsequent isolation period in separate buildings for virus-safe quarantine [Figure 1A]. We found that 695 cases of 2212 (31.4%) were viral RNA negative in both the hospitalization and isolation stages [Figure 1B]. Despite their proportions varying month-by-month, such individuals were observed monthly [Figure 1C], suggesting frequent occurrences. Notably, patients with obvious chest computed tomography abnormalities were defined as moderate, according to the essential criteria for COVID-19 diagnosis. Among the 695 all-negative viral RNA cases, the number of asymptomatic cases increased to 515 (74.1%). There were 147 (21.2%) and 33 (4.7%) moderate and mild cases, respectively [Figure 1D]. Moderate patients with visible lung damage but undetectable viral RNA were in the recovery period when the virus was cleared and the lung damage was improving. Unfortunately, their symptoms were unavailable because of lack of convincing records before admission to our hospital. This high percentage of cases with undetectable viral RNA occupied precious medical beds and consumed a substantial amount of medical resources. Therefore, strategies to precisely identify and classify these individuals, and release them outside of the closed-loop patient management system will markedly relieve the medical burden.
Next, we investigated the relationship between all viral negative cases and length of hospitalization in every case. According to the Chinese Diagnosis and Treatment Protocol for COVID-19 Patients (Trial Version 8), suspected patients can be confirmed with a positive real-time polymerase chain reaction detection of the novel coronavirus nucleic acid and should be transferred to the hospital to receive treatment. All individuals who enter Guangzhou, China, from abroad were subjected to viral RNA detection. Patients who tested positive for viral RNA were transferred to Guangzhou Eighth People’s Hospital. In the hospital, all admitted patients had their first viral RNA detection immediately after admission (on day 0). Their nasopharyngeal samples were collected at 2- or 3-day intervals, depending on their viral titers, to monitor the viral load change in a timely manner. According to these criteria, patients with two consecutive viral RNA negative more than 24 hours apart can be discharged to leave the hospital.
We found that 1003 cases (of all 2212 imported cases, 45.3%) were discharged within 5 days (termed ultrashort hospitalization) [Figure 2A and Table 1]. Six hundred one patients (59.9%) in this group tested negative on day 0, 2–3, and 3–5 for the first, second, and third viral detection [Figure 2B]. In addition, 307 cases (30.6%) were retest positive during the isolated quarantine period. The other 95 cases (9.5%) had one or two viral RNA positive tests and two viral RNA negative tests during the hospitalization period.
Table 1 -
The distribution of hospitalization time of imported COVID-19 cases in each month in Guangzhou, China, 2021
Finally, we observed the viral titers among the different groups. Among the remaining 307 cases with viral RNA retest positivity, 148 (48.2%) were only positive at one time point during the isolation period, and 98.0% (145/148) of their peak viral RNA was over Ct = 33 cycles [Figure 2C and 2D]. The remaining 159 cases (51.8%) showed two or more viral RNA positive tests during the isolation stage [Figure 2C], and 95.0% of their peak viral RNA (151/159) was more than Ct = 33 cycles [Figure 2D]. We analyzed dynamic viral RNA changes in 95 cases with detectable viral RNA during the in-hospital period [Figure 2E]. Only two cases (red) had viral RNA levels less than Ct = 30 cycles, and only four cases (blue) had viral RNA levels between 30 and 33 cycles. Altogether, our results indicated that all cases had low levels of viral RNA.
Our systemic analysis of all 2212 imported cases infected with SARS-CoV-2 over the entire year 2021 revealed that approximately 31.4% of patients (695/2212) were viral RNA test negative, suggesting that all those cases were inessential to subject to centralized treatment and isolation. During the infection life cycle, SARS-CoV-2 goes through incubation, increases, plateaus, declines, disappears, or sometimes retests positive. We postulate that all negative viral RNA test imported cases were already at the end of disappearing or retest positive when confirmed at the entry into the Chinese customs or retest positive in the isolated hotels. The sensitive PCR test caught their last viral RNA positive, and they were sent to the hospital to receive treatment.
Our study indicated that rigorous screening in customs and isolation hotels effectively identified individuals with low viral RNA levels.
Combining the initial three to four viral RNA tests provides a feasible strategy for identifying all negative viral RNA test patients if all consecutive tests are negative. The incubation period for Delta or Omicron has been shortened to less than 5 days.[4,5] In addition, the infectious viral particle has been found to persist for 2 weeks when the viral titer is greater than 10e5 copies/mL (equal to Ct = 29–32).[6–8] Therefore, in our study, 5 days and three viral RNA surveillance tests could confirm whether the viral concentration was in the early increase stage or the late disappearance. In the early stage, a significant viral increase occurs. Otherwise, if all three to four viral RNA tests are negative, the individual could be diagnosed with a late-stage infection, and they should be discharged in time.
Our study had some limitations. First, this was a single-center retrospective study. Second, the cases in this study were mainly of the SARS-CoV-2 Delta variant. Nonetheless, the study has provided insight into the clinical characteristics of admitted patients who were all viral RNA test negative from admission to discharge to the final release from quarantine, and the retest positive cases had low levels of viral RNA.
In conclusion, a high percentage of imported COVID-19 cases (more than 1/3) admitted to Guangzhou Eighth People’s Hospital were viral RNA negative from the beginning to the final release after quarantine isolation, occupying precious medical resources for infectious diseases. We recommend that the hospital observation period for polymerase chain reaction–confirmed cases abroad be shortened to no more than 5 days to save medical resources, especially in dealing with large epidemics.
The authors thank all the patients and all the people involved in treating COVID-19, including all healthcare workers who provide care for patients with COVID-19 and are involved in the diagnosis and management of COVID-19 patients and those who trace and quarantine the contacts.
Xilong Deng, Xiaoping Tang, Fengyu Hu, Feng Li, and Jinxin Liu developed the conceptual ideas and designed the study. Zhiwei Xie, Guofang Tang, and Lu Li performed the experiments and statistical analysis. Jingrong Shi provided the essential assistance through experiments. Qingxin Gan, Jingyan Tang, Xiaowen Zheng, Huimin Zeng, Chuyu Zhang, Sisi Chen, Jianping Cui, Zishi Lin, Lihua Lin, and Youxia Li were responsible for sample collection. All authors provided scientific expertise and the interpretation of data for the work. Feng Li drafted the manuscript. All authors contributed to critical revision of the manuscript for important intellectual content. All authors reviewed and approved the final version of the report.
This study was supported by the Emergency Key Program of Guangzhou Laboratory (EKPG21-29 and EKPG21-31), Zhongnanshan Medical Foundation of Guangdong Province (ZNSA-2021004), the Emergency Grants for SARS‐CoV‐2 Prevention and Control of Guangdong Province (Nos.2022A1111090002 and 2021A1111110001), and Guangzhou Science and Technology Plan Project (No.202201020338).
Conflicts of Interest
Data Available Statement
The data sets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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