Prolonged SARS‐CoV‐2 RNA shedding: Not a rare phenomenon

Abstract

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic globally.1 As of 18 April, it had infected over 2 million people worldwide. Recently, a study reported that the median duration of SARS-CoV-2 RNA shedding in 113 patients was 17 days from symptom onset in Zhejiang and Shenzhen centers.2 In Wuhan, where the coronavirus disease 2019 (COVID-19) first started, the duration of the infection and clinical characteristics of the patients remain unknown. Herein, we studied the clinical characteristics of 36 confirmed COVID-19 patients who continued to shed viral RNA for longer than 30 days. The 378 patients diagnosed with COVID-19 based on the New Coronavirus Pneumonia Prevention and Control Program (5th edition) published by the National Health Commission of China,3 were admitted to the 4th Infectious Disease Department in Wuhan Huoshenshan Hospital from 11 February to 11 April 2020. We searched their electronic medical records and found that their duration of SARS-CoV-2 RNA shedding was longer than 30 days. The 36 patients were tested for SARS-CoV-2 using the real-time reverse transcriptase polymerase chain reaction (RT-PCR) test, on samples collected from the respiratory tract using the Chinese Center for Disease Control and Prevention (CDC) recommended Kit (BioGerm, Shanghai, China), and following World Health Organization (WHO) guidelines for qRT-PCR.4 The median age of the patients was 57.5 years (interquartile range [IQR] 52-65) and 11.1% of them were below 40 years old. Among the patients, 13 (36.1%) were females. Most patients had associated comorbidities (22 [61.1%]), including cardiovascular diseases like hypertension and coronary heart disease (16 [44.4%]), metabolic diseases like diabetes and gout (7 [19.4%]), and chronic respiratory diseases like chronic bronchitis (3 [8.3%]). In addition, some patients had more than one comorbidity. On admission, 33 (91.7%) and 3 (8.3%) patients had mild and severe COVID-19, respectively. A recent report by Yang et al5 described a patient whose clinical course lasted for more than 2 months. However, in our study, prolonged viral RNA shedding even after symptomatic relief was not rare, and the median duration of viral RNA shedding was 53.5 days (IQR 47.75-60.5). The longest duration of viral RNA shedding could be 83 days. We divided the patients into two groups: early-onset group whose symptoms started before 1 February 2020 and late-onset group whose symptoms started after 1 February 2020. Compared to the late-onset group, the patients in the early-onset group had longer durations of viral shedding and more severe illnesses. SARS-CoV-2 immunoglobulin M (IgM) and IgG antibodies were analyzed by chemiluminescent immunoassay following the protocol of the manufacture (Shenzhen Yahuilong Biotechnology Co, Ltd). Although the IgM level reached its peak as in SARS-CoV,6 it could remain persistently high in these patients even until the ninth week (Figure 1). The high levels of IgM indicated the duration of viral infection and may be related to the prolonged viral RNA shedding. Most of the patients received antiviral therapy at the beginning of the infection for at least 1 week, including arbidol (34 [91.9%]), ribavirin (1 [2.7%]), and remdesivir (2 [5.4%]). In addition, 17 patients received antiviral treatment again at the final stage, due to the prolonged viral RNA shedding. Among them, 13 patients received chloroquine phosphate therapy and 4 patients received chloroquine and favipiravir combined therapy for at least 5 days until their nucleic acid test turned negative. Although the mortality caused by COVID-19 is lower than that by SARS and MERS, the infectivity and transmissibility of the virus is higher.7 A definite and an effective treatment for the disease is still under investigation and the targeted vaccine is undergoing clinical trials. The most effective way to control the disease spread is by the isolation of patients. According to our results, prolonged viral RNA shedding is not a rare phenomenon regardless of symptomatic relief. Moreover, a study by Xiao et al8 showed a high rate of patients got positive viral RNA nucleic acid tests again after two consecutive negative tests. Therefore, a longer observation period for COVID-19 patients is necessary independent of symptomatic relief and even when the patients have met the discharge standard—two consecutive negative nucleic acid tests. The IgM titer test may be an effective supplementary test. A study reported that viral RNA shedding from asymptomatic patients was similar to that of other patients.9 And Jiang et al10 even described an asymptomatic patient whose viral detection was positive in stools for 42 days but persistent negative in throat samples. Therefore, further studies are necessary to investigate the infectivity of these prolonged-RNA-shedding patients at the later stage of the clinical course and their viral RNA shedding in stools, and the use of some antiviral