Little is known about Subgenomic RNA (sgRNA) dynamics in patients with Coronavirus diseases 2019 (COVID19). We collected 147 throat swabs, 74 gut swabs and 46 plasma samples from 117 COVID-19 patients recruited in the LOTUS China trial (ChiCTR2000029308) and compared E and orf7a sgRNA load in patients with different illness duration, outcome, and comorbidities. Both sgRNAs were detected in all the three types of samples, with longest duration of 25, 13, and 17 days for E sgRNA, and 32, 28, and 17 days for orf7a sgRNA in throat, gut, and plasma, respectively. A total of 95% (57/60) of patients had no E sgRNA detected after 10 days post treatment, though 86% of them were still E RNA positive. High correlation on titer was observed between sgRNA encoding E and orf7a gene. sgRNA showed similar variation in the standard care and Lopinavir-Ritonavir group. Patients with diabetes and heart diseases showed higher pharyngeal E sgRNA at the first day (P = 0.016 and 0.013, respectively) but no difference at five days after treatment, compared with patients without such commodities. Patients with hypertension and cerebrovascular diseases showed no difference in the pharyngeal sgRNA levels at both one and five days after treatment, compared with patients without these two commodities. E sgRNA levels in the initial infection showed no correlation with the serum antibody against spike, nucleoprotein, and receptor binding domains at ten days later. sgRNA lasted a long period in COVID-19 patients and might have little effect on humoral response.