Persistence and Clearance of Viral RNA in 2019 Novel Coronavirus Disease Rehabilitation Patients
The 2019 novel coronavirus (2019-nCoV), identified as the causative agent of the COVID-19 pandemic, has posed significant challenges to global public health. Understanding the persistence and clearance of viral RNA in different body fluids and excreta of patients is critical for managing the disease, particularly during the convalescent phase. This study provides valuable insights into the duration of viral RNA detection in various specimens, including oropharyngeal swabs, stool, urine, and serum, and examines factors influencing viral clearance, such as immune response and glucocorticoid treatment.
Introduction
The transmission of 2019-nCoV is primarily driven by the presence of the virus in respiratory secretions, but emerging evidence suggests that viral RNA can also be detected in other body fluids and excreta, such as stool and urine. This raises concerns about potential alternative routes of transmission, including fecal-oral and vertical transmission. Current guidelines recommend isolating patients until they have two successive negative RT-PCR results for respiratory specimens, but the persistence of viral RNA in other samples remains unclear. This study aims to elucidate the clearance time of viral RNA in different specimens and identify factors that may influence this process.
Methods
This retrospective study analyzed clinical data and laboratory test results from 66 convalescent COVID-19 patients admitted to the Shanghai Public Health Clinical Center between January 20, 2020, and February 10, 2020. Convalescent patients were defined as those who had recovered from fever and respiratory symptoms and had two consecutive negative RT-PCR results for viral RNA from oropharyngeal swabs, with at least a 24-hour interval between tests. The study collected and analyzed RT-PCR results from oropharyngeal swabs, stool, urine, and serum samples. Additionally, the effects of CD4+ T lymphocyte counts, inflammatory markers, and glucocorticoid treatment on viral RNA clearance were examined.
Results
Demographics and Laboratory Findings
The study included 66 convalescent patients, comprising 28 women (42.4%) and 38 men (57.6%), with a median age of 44.0 years (range: 34.0–62.0 years). Inflammatory markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT), were elevated at admission but decreased significantly with treatment. The median ESR decreased from 70.0 mm/h to 44.0 mm/h, CRP from 8.4 mg/L to 0.5 mg/L, and PCT from 0.03 ng/mL to 0.02 ng/mL.
Viral RNA Detection in Different Specimens
The median time from symptom onset to the first negative RT-PCR result for oropharyngeal swabs was 9.5 days (range: 6.0–11.0 days). By February 10, 2020, 11 patients (16.7%) still tested positive for viral RNA in stool specimens, while the remaining 55 patients had negative stool results after a median duration of 11.0 days (range: 9.0–16.0 days) from symptom onset. Among these 55 patients, 43 (78.2%) had a longer duration of viral RNA detection in stool compared to oropharyngeal swabs, with a median delay of 2.0 days (range: 1.0–4.0 days). Viral RNA was detected in urine samples of only 4 out of 58 patients (6.9%), and in three cases, urine samples remained positive after oropharyngeal swabs turned negative. None of the 14 serum samples tested positive for viral RNA.
Factors Influencing Viral RNA Clearance
A multiple linear regression analysis revealed that the absolute count of CD4+ T lymphocytes was significantly associated with the duration of viral RNA detection in stool samples. Patients with lower CD4+ T lymphocyte counts had a longer duration of viral RNA clearance in stool (t = -2.699, P = 0.010). Inflammatory markers such as ESR, CRP, and PCT did not show a significant correlation with viral RNA clearance in stool.
Glucocorticoid treatment was associated with delayed viral RNA clearance. Patients who received glucocorticoids had a longer median duration of viral RNA detection in oropharyngeal swabs (15.0 days vs. 8.0 days, t = 2.550, P = 0.013) and stool samples (20.0 days vs. 11.0 days, t = 4.631, P < 0.001) compared to those who did not receive glucocorticoids. There was no significant difference in inflammatory markers between patients with positive and negative stool viral RNA results.
Discussion
The study highlights the prolonged detection of viral RNA in stool specimens compared to oropharyngeal swabs, suggesting that the virus may persist in the gastrointestinal tract even after respiratory samples test negative. This finding underscores the importance of monitoring fecal samples during the convalescent phase to mitigate the risk of fecal-oral transmission. The detection of viral RNA in urine samples, although rare, further emphasizes the need for comprehensive testing to prevent potential alternative routes of transmission.
Glucocorticoid treatment was found to delay viral RNA clearance, particularly in stool samples. This observation aligns with previous studies that suggest glucocorticoids may suppress immune responses, thereby prolonging viral persistence. Given this, the use of glucocorticoids should be carefully considered, especially in mild cases of COVID-19, to avoid delaying viral clearance and potentially increasing the risk of transmission.
The study also highlights the role of host immunity, particularly CD4+ T lymphocytes, in viral RNA clearance. Lower CD4+ T lymphocyte counts were associated with longer durations of viral RNA detection in stool, suggesting that cellular immunity plays a critical role in controlling viral replication and clearance. This finding underscores the importance of monitoring immune responses in COVID-19 patients to predict disease progression and recovery.
Conclusion
In conclusion, the persistence of viral RNA in stool specimens during the convalescent phase of COVID-19 highlights the need for comprehensive testing and monitoring of fecal samples. Glucocorticoid treatment should be used judiciously, as it may delay viral RNA clearance and prolong infectivity. The role of CD4+ T lymphocytes in viral clearance further emphasizes the importance of host immunity in managing COVID-19. These findings provide valuable insights for improving patient management and reducing the risk of transmission during the convalescent phase.
doi.org/10.1097/CM9.0000000000000774
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