We conducted a retrospective analysis of the guidelines on COVID-19 management. Included documents were published before April 1, 2020; were written in English or had an English translation available; were published in journals or on the websites of scientific societies, regulatory bodies, or scientific institutions; considered antiviral therapies; and contained a recommendation (or recommendations) for clinicians. Those documents were defined for the purpose of this study as: 1) a statement with recommendation, advice, suggestions, or tips; and/or 2) a statement that it is not possible to provide any recommendation because of the lack of data considered adequate. Adaptations of existing guidelines were also included. Papers indexed as original articles or reviews were excluded.
We performed the search for relevant documents between May 15 and 22, 2020, using MEDLINE and Embase databases as well as Google Search. Search strategies are presented in Supplementary Material. An additional search was performed to detect if any update of the previously identified guidelines had been released within the 2 months after the publication of the first RCT on antiviral COVID-19 treatment. Details on search strategy are presented in Additional File 1. Identified documents were screened based on the title and abstract (database search) or full-text documents (Google search). After duplicate removal, full-text documents were assessed for eligibility by two authors (FM and WL) independently (flowchart available in Additional file 2). Any discrepancies between evaluators during the study selection process were resolved by discussion.
The quality of the guidelines was assessed using the AGREE II-Global Rating Scale Instrument (AGREE II-GRS). This scale has 4 core items (process of development, presentation style, completeness of reporting and clinical validity), each rated from 1 (lowest quality) to 7 (highest quality). Additionally, there is an overall assessments of the guideline quality, similarly ranging from 1 (lowest quality) to 7 (highest quality) and two additional items, based on users’ answer to questions whether they would recommend the guideline for use in practice and whether they would make use of a guideline of that quality in their own professional decisions (both rated from 1 = strongly disagree to 7 = strongly agree). Each document was assessed by two appraisers and the mean scores are reported.
In addition, to characterise rigour of guideline development more precisely we assessed included documents using series of dichotomous criteria based on the domain 3 of the AGREE II tool itself and World Health Organization (WHO) standards [2, 11, 12]. Specifically, we verified if the assessed documents: used existing methodology of guidelines development; contained information on formation of the working group or searching for evidence; provided strength of recommendations and references to recommendations; included conflict of interest (COI) information; rated quality of evidence; updated document when new evidence was available (which we defined as within two month from publication of the first RCT (lopinavir/ritonavir efficacy in COVID-19 ) as well as sought opinion of external reviewers. We classified documents as containing strong recommendations (using phrases “is recommended”, “should be used”) or weak recommendations (suggestions, using phrases such as “may be used, consider the use” etc) or no recommendation for use of antiviral therapy (recommendation not to use antivirals outside clinical trials or a statement that evidence is lacking). Detailed information on data extracted is provided in Supplementary Information.
Two authors (FM and WL) extracted the data, and assessed the quality of CPGs (data extracted are listed in Additional File 3). Any disagreements were resolved by discussion.
Statistical analysis was performed using the Statistica v13.3 software (Tibco Software Inc.). Assumption of normality was verified with the Shapiro–Wilk and Kolmogorov–Smirnov tests. Between-group comparisons were made with the Kruskal–Wallis analysis of variance, Mann–Whitney, and χ2 test, as appropriate. To identify variables independently associated with the recommendations for antiviral therapy for SARS-CoV-2, a multiple logistic regression analysis was used, with models built by adding subsequent variables. The presence of recommendations for antiviral therapy for SARS-CoV-2 was the dependent variable and the type of document, mode of publication and issuing institution were use as covariates in the first model, with the following variables added to subsequent models in a stepwise manner: using existing methodology of guidelines development, the presence of information on formation of the working group, description of search for evidence, the presence of COI information and rated quality of evidence. We considered a p value of less than 0.05 significant.