Sequelae of long COVID, known and unknown: A review of updated information.

Over three years have passed since the COVID-19 pandemic started. The dangerousness and impact of COVID-19 should definitely not be ignored or underestimated. Other than the symptoms of acute infection, the long-term symptoms associated with SARS-CoV-2 infection, which are referred to here as "sequelae of long COVID (LC)", are also a conspicuous global public health concern. Although such sequelae were well-documented, the understanding of and insights regarding LC-related sequelae remain inadequate due to the limitations of previous studies (the follow-up, methodological flaws, heterogeneity among studies, etc.). Notably, robust evidence regarding diagnosis and treatment of certain LC sequelae remain insufficient and has been a stumbling block to better management of these patients. This awkward situation motivated us to conduct this review. Here, we comprehensively reviewed the updated information, particularly focusing on clinical issues. We attempt to provide the latest information regarding LC-related sequelae by systematically reviewing the involvement of main organ systems. We also propose paths for future exploration based on available knowledge and the authors' clinical experience. We believe that these take-home messages will be helpful to gain insights into LC and ultimately benefit clinical practice in treating LC-related sequelae.

Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial.

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.