ABSTRACT
BACKGROUND: The clinical characteristics and treatment of patients who tested positive for COVID-19 after recovery remained elusive. Effective antiviral therapy is important for tackling these patients. We assessed the efficacy and safety of favipiravir for treating these patients. METHODS: This is a multicenter, open-label, randomized controlled trial in SARS-CoV-2 RNA re-positive patients. Patients were randomly assigned in a 2:1 ratio to receive either favipiravir, in addition to standard care, or standard care alone. The primary outcome was time to achieve a consecutive twice (at intervals of more than 24 h) negative RT-PCR result for SARS-CoV-2 RNA in nasopharyngeal swab and sputum sample. RESULTS: Between March 27 and May 9, 2020, 55 patients underwent randomization; 36 were assigned to the favipiravir group and 19 were assigned to the control group. Favipiravir group had a significantly shorter time from start of study treatment to negative nasopharyngeal swab and sputum than control group (median 17 vs. 26 days); hazard ratio 2.1 (95% CI [1.1-4.0], p = 0.038). The proportion of virus shedding in favipiravir group was higher than control group (80.6% [29/36] vs. 52.6% [10/19], p = 0.030, respectively). C-reactive protein decreased significantly after treatment in the favipiravir group (p = 0.016). The adverse events were generally mild and self-limiting. CONCLUSION: Favipiravir was safe and superior to control in shortening the duration of viral shedding in SARS-CoV-2 RNA recurrent positive after discharge. However, a larger scale and randomized, double-blind, placebo-controlled trial is required to confirm our conclusion.
Subject(s)
Amides/administration & dosage , Antiviral Agents/administration & dosage , COVID-19 Drug Treatment , Pyrazines/administration & dosage , Reinfection/drug therapy , Administration, Oral , Adult , Aged , Amides/adverse effects , Antiviral Agents/adverse effects , COVID-19/blood , Female , Humans , Lymphocyte Subsets/drug effects , Male , Middle Aged , Patient Discharge , Pyrazines/adverse effects , RNA, Viral/analysis , RNA, Viral/drug effects , Reinfection/blood , SARS-CoV-2/drug effects , Treatment OutcomeABSTRACT
BACKGROUND: The management of discharge COVID-19 patients with recurrent positive SARS-CoV-2 RNA is challenging. However, there are fewer scientific dissertations about the risk of recurrent positive. The aim of this study was to explore the relationship between SARS-COV-2 RNA positive duration (SPD) and the risk of recurrent positive. METHODS: This case-control multi-center study enrolled participants from 8 Chinese hospital including 411 participants (recurrent positive 241). Using unadjusted and multivariate-adjusted logistic regression analyses, generalized additive model with a smooth curve fitting, we evaluated the associations between SPD and risk of recurrent positive. Besides, subgroup analyses were performed to explore the potential interactions. RESULTS: Among recurrent positive patients, there were 121 females (50.2%), median age was 50 years old [interquartile range (IQR): 38-63]. In non-adjusted model and adjusted model, SPD was associated with an increased risk of recurrent positive (fully-adjusted model: OR = 1.05, 95% CI: 1.02-1.08, P = 0.001); the curve fitting was not significant (P = 0.286). Comparing with SPD < 14 days, the risk of recurrent positive in SPD > 28 days was risen substantially (OR = 3.09, 95% CI: 1.44-6.63, P = 0.004). Interaction and stratified analyses showed greater effect estimates of SPD and risk of recurrent positive in the hypertension, low monocyte count and percentage patients (P for interaction = 0.008, 0.002, 0.036, respectively). CONCLUSION: SPD was associated with a higher risk of recurrent positive and especially SPD > 28 day had a two-fold increase in the relative risk of re-positive as compared with SPD < 14 day. What's more, the risk may be higher among those with hypertension and lower monocyte count or percentage.