Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: an evidence-based clinical practice guideline (updated version)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients

Systematic review of the registered clinical trials for coronavirus disease 2019 (COVID-19).

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics. METHODS: This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. RESULTS: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60-200), and the median length of the trial periods was 179 d (IQR: 94-366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low. CONCLUSIONS: Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.