Associations of viral ribonucleic acid (RNA) shedding patterns with clinical illness and immune responses in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) infection

Lee, Pei Hua; Tay, Woo Chiao; Sutjipto, Stephanie; Fong, Siew‐Wai; Ong, Sean Wei Xiang; Wei, Wycliff Enli; Chan, Yi‐Hao; Ling, Li Min; Young, Barnaby E; Toh, Matthias Paul HS; Renia, Laurent; Ng, Lisa FP; Leo, Yee‐Sin; Lye, David C; Lee, Tau Hong

OBJECTIVES: A wide range of duration of viral RNA shedding in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has been observed. We aimed to investigate factors associated with prolonged and intermittent viral RNA shedding in a retrospective cohort of symptomatic COVID‐19 patients. METHODS: Demographic, clinical and laboratory data from hospitalised COVID‐19 patients from a single centre with two consecutive negative respiratory reverse transcription‐polymerase chain reaction (RT‐PCR) results were extracted from electronic medical records. Kaplan–Meier survival curve analysis was used to assess the effect of clinical characteristics on the duration and pattern of shedding. Plasma levels of immune mediators were measured using Luminex multiplex microbead‐based immunoassay. RESULTS: There were 201 symptomatic patients included. Median age was 49 years (interquartile range 16–61), and 52.2% were male. Median RNA shedding was 14 days (IQR 9–18). Intermittent shedding was observed in 77 (38.3%). We did not identify any factor associated with prolonged or intermittent viral RNA shedding. Duration of shedding was inversely correlated with plasma levels of T‐cell cytokines IL‐1β and IL‐17A at the initial phase of infection, and patients had lower levels of pro‐inflammatory cytokines during intermittent shedding. CONCLUSIONS: Less active T‐cell responses at the initial phase of infection were associated with prolonged viral RNA shedding, suggesting that early immune responses are beneficial to control viral load and prevent viral RNA shedding. Intermittent shedding is common and may explain re‐detection of viral RNA in recovered patients.