Objective To comprehensively evaluate the quality of the non-randomized studies on the effects of published interventions into the Chemoprophylaxis, diagnosis, treatments, and dis-charge management of COVID-19: an evidence-based clinical practice guideline (updated version). 

Methods The well-established guideline search strategy was used in this study. An electronic litera-ture search was conducted using PubMed, Embase, the Cochrane Library, CNKI, Wanfang Database and major medical journals which included the topics of infection or respiration, preprint platforms and clinical trial registries from December 1, 2019, to July 8, 2020. The language was limited to Chi-nese and English. Non-randomized intervention studies of pharmacotherapies for the prevention and treatment of COVID-19 were sought and included, and methodological quality assessment was con-ducted using the f ROBINS-I tool. 

Results A total of 40 non-randomized intervention studies were retrieved, including 20 antiviral drug intervention studies, 16 immunotherapy intervention studies and 4 traditional Chinese medicine intervention studies. Our evaluation showed that the overall risk of bias in all 40 studies was moderate to serious, and 15 of them had a "serious" overall risk of bias. Two domains (bias due to confounding and bias due to deviations from intended interventions) had a high risk of bias, mainly because of the poor control of baseline confounding factors, time-varying confounding factors and important intergroup variations of intervention measures. 

Conclusions The overall quality of existing non-randomized intervention studies on pharmacotherapy for the preven-tion and treatment of COVID-19 is poor, and some recommendations are inconclusive. Large, pro-spective studies and randomized controlled trials with a rigorous design are needed to improve the quality of evidence.

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