Pan-American Guidelines for the Treatment of SARS-CoV-2/COVID-19: A Joint Evidence-Based Guideline of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API) (preprint)

Background Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations. Considering the particular impact of COVID-19 in the Americas, this document aims to present recommendations for the pharmacological treatment of COVID-19 specific to this population.Method Fifteen experts, members of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API) make up the panel responsible for developing this guideline. Questions were formulated regarding prophylaxis and treatment of COVID-19 in outpatient and inpatient settings. The outcomes considered in decision-making were mortality, hospitalisation, need for mechanical ventilation, symptomatic COVID-19 episodes, and adverse events. In addition, a systematic review of randomised controlled trials was conducted. The quality of evidence assessment and guideline development process followed the GRADE system.Results Nine technologies were evaluated, and ten recommendations were made, including the use of tixagevimab + cilgavimab in the prophylaxis of COVID-19, tixagevimab + cilgavimab, molnupiravir, nirmatrelvir + ritonavir, and remdesivir in the treatment of outpatients, and remdesivir, baricitinib, and tocilizumab in the treatment of hospitalised patients with severe COVID-19. The use of hydroxychloroquine or chloroquine and ivermectin was discouraged.Conclusion This guideline provides recommendations for treating patients in the Americas following the principles of evidence-based medicine. The recommendations present a set of drugs that have proven effective in the prophylaxis and treatment of COVID-19, emphasising the strong recommendation for the use of nirmatrelvir/ritonavir in outpatients as the lack of benefit from the use of hydroxychloroquine and ivermectin.

Knowledge mobilization activities to support decision-making by youth, parents, and adults using a systematic and living map of evidence and recommendations on COVID-19: protocol for a randomized controlled trial (preprint)

IntroductionThe COVID-19 pandemic underlined that guidelines and recommendations must be made more accessible and more understandable to the general public, including adults, parents, and youth, to improve health outcomes. The objective of this study is to evaluate, quantify, and compare the publics (youth, parents, and adult populations) understanding, usability, satisfaction, intention to implement, and preference for different ways of presenting COVID-19 health recommendations derived from the COVID-19 Living Map of Recommendations and Gateway to Contextualization (herein referred to as the RecMap). Methods and AnalysisThis is a protocol for a multi-method study. We will conduct pragmatic allocation-concealed, blinded superiority randomized controlled trials (RCT) in three populations to test alternative formats of presenting health recommendations: adults (21 years of age or older), parents (18 years or above and are a parent or legal guardian of a child under 18 years old), and youth (15 to 24 years old), with at least 240 participants in each population. The research will consist of a randomized online survey and an optional one-on-one interview. Prior to initiating the RCT, our interventions will have been refined with relevant stakeholder input. In each population group, the intervention arm will receive a plain language recommendation (PLR) format while the control arm will receive the corresponding original recommendation format as originally published by the guideline organizations (herein referred to as Standard Language Version). Our primary outcome is understanding, and our secondary outcomes are accessibility and usability, satisfaction, intended behavior, and preference for the two recommendation formats. Each populations results will be analyzed separately. However, we are planning a meta-analysis of the results across populations, and will also explore potential interaction and subgroup effects within each population. At the end of each survey, participants will be invited to participate in a one-on-one, virtual semi-structured interview to explore their user experience and their learning preferences and future research. All interviews will be transcribed and analyzed using the principles of thematic analysis and a hybrid inductive and deductive approach. Iterative member checking, triangulation, interpretation, and saturation of themes will be sought to enhance reliability. Ethics and DisseminationThrough Clinical Trials Ontario (CTO), the Hamilton Integrated Research Ethics Board has reviewed and approved this protocol (Project ID: 3856). The University of Alberta has approved the parent portion of the trial (Project ID:00114894). All potential participants will be required to provide informed consent. The findings from this study will be disseminated through open-access publications in peer-reviewed journals and using social media. Strengths and limitations of this studyO_LIWe are following a multi-method approach: randomized controlled trials and qualitative interviews. The qualitative results will supplement and help explain our quantitative findings. C_LIO_LIThis protocol is reported in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT), which enhances transparency and completeness. The trials use previously validated outcomes from similar trials. This will strengthen the credibility of our results. C_LIO_LIOur study is testing an optimized plain language recommendation format, which makes our intervention relevant to our stakeholder groups, and is recruiting internationally, which ensures the inclusion of a diverse population. Recruitment will take place online using social media, and data will be collected using an online survey. This allows for self-selection and limits accessibility to those who have no or limited digital access, which in turn limits generalizability. C_LIO_LIWhile the recommendations are offered in multiple languages through the RecMap, the study is only testing English plain language recommendation summaries. C_LI

Hydroxychloroquine alone or in combination with azithromycin to prevent major clinical events in hospitalised patients with coronavirus infection (COVID-19): rationale and design of a randomised, controlled clinical trial (preprint)

Introduction: Hydroxychloroquine and its combination with azithromycin have been suggested to improve viral clearance in patients with COVID-19, but its effect on clinical outcomes remains uncertain. Methods and analysis: We describe the rationale and design of an open-label pragmatic multicentre randomised (concealed) clinical trial of 7 days of hydroxychloroquine (400 mg BID) plus azithromycin (500 mg once daily), hydroxychloroquine 400 mg BID, or standard of care for moderately severe hospitalised patients with suspected or confirmed COVID-19 (in-patients with up to 4L/minute oxygen supply through nasal catheter). Patients are randomised in around 50 recruiting sites and we plan to enrol 630 patients with COVID-19. The primary endpoint is a 7-level ordinal scale measured at 15-days: 1)not hospitalised, without limitations on activities; 2)not hospitalised, with limitations on activities; 3)hospitalised, not using supplementary oxygen; 4)hospitalised, using supplementary oxygen; 5)hospitalised, using high-flow nasal cannula or non-invasive ventilation; 6)hospitalised, on mechanical ventilation; 7)death. Secondary endpoints are the ordinal scale at 7 days, need for mechanical ventilation and rescue therapies during 15 days, need of high-flow nasal cannula or non-invasive ventilation during 15 days, length of hospital stay, in-hospital mortality, thromboembolic events, occurrence of acute kidney injury, and number of days free of respiratory support at 15 days. Secondary safety outcomes include prolongation of QT interval on electrocardiogram, ventricular arrhythmias, and liver toxicity. The main analysis will consider all patients with confirmed COVID-19 in the groups they were randomly assigned. Ethics and dissemination: This study has been approved by Brazil's National Ethic Committee (CONEP) and National Health Surveillance Agency (ANVISA). An independent data monitoring committee will perform interim analyses and evaluate adverse events throughout the trial. Results will be submitted for publication after enrolment and follow-up are complete, as well as presented and reported to local health agencies. ClinicalTrials.gov identifier: NCT04322123