2.1. Study Analysis
The initial survey of the literature identified 2756 reports (2066 from Scopus and 690 from PubMed). Then, 293 the duplicates between the two databases were eliminated and were considered only one at a time, resulting in 2463 articles. After the primary screening based on titles and abstracts, 959 manuscripts were excluded since they did not fulfil the inclusion criteria or were off-topic. Finally, 1504 articles were thoroughly analyzed and among these, 1442 were excluded. The analysis of the reference lists from some selected items led to the inclusion of an extra 71 appropriate articles, after titles, abstracts, and full-text study. In total, 133 papers were selected for data extraction. A flowchart illustrating the steps of the study selection is shown in Figure 2.
In our review, the articles included were also analyzed in relation to the year of publication and the experimental model used. Regarding the chronology of the publications, most of the articles were published in the last decade. The high peaks correspond to the proportional number of papers on antiviral activity in 2020; this result is consistent with the actual increasing interest towards the role of HCQ as a possible therapeutic strategy in the current COVID-19 sanitary emergency. HCQ alone, or in combination with other drugs, was used in various types of infections. HIV and COVID-19 were the most cited, with 10 and 7 reports each, respectively. Our systematic review included 49 preclinical studies and 84 clinical trials. The considered in vivo studies were carried out using allograft or xenograft models. The most important outcomes of the review are graphically illustrated in Figure 3.
The assessment of bias risk based on a checklist adapted from the Cochrane Handbook for Systematic Reviews of Interventions is reported in Figure 4. The number of high-risk reports is due to the case reports considered.