Original Title: COVID-19 : usage optimal des traitements pharmacologiques

Authors' objectives: In Quebec, according to the most recent data published in Winter 2024, more than 1.4 million people contracted coronavirus (COVID-19) disease, of whom more than 20,000 died. Unlike other respiratory viruses, severe acute respiratory syndrome Coronavirus 2 is not, to date, a seasonal virus. In fact, cases of infection and hospitalization associated with COVID-19 persist throughout the year. Between March 2020 and February 2024, the Institut national d'excellence en santé et en services sociaux (INESSS), which has been mobilized since the start of the pandemic, conducted work that led to the development of several clinical tools, continuously updated in line with advances in knowledge, on drugs administered for the pharmacological treatment of people with COVID-19. Considering the end of continuous scientific monitoring of COVID-19 treatments, the rapid response method used during the pandemic and the multiplicity of these clinical tools, the INESSS has decided to conduct work, according to its usual scientific process, in order to publish an optimal use guide covering all treatments.

Authors' results and conclusions: RESULTS (#1 RECOGNIZING THE RISK OF COVID-19 COMPLICATIONS FOR OPTIMIZED THERAPEUTIC MANAGEMENT): As vaccination waves and campaigns have evolved, so have the characteristics of those most likely to develop complications from COVID-19. In fact, immunity conferred by previous infection and/or vaccination against SARS-CoV-2 are factors that contribute to reducing the risk of COVID-19 complications, although the further one is from the last vaccine dose, or the last infection, the weaker the protection. Because of the large proportion of people immunized by vaccination or previous infections, the likelihood of developing serious complications from the infection has been greatly reduced in the population since Omicron, and this trend is continuing. For many, a simple supportive treatment will be required, while for others, depending on the anticipated risk level of complications, an antiviral may be administered. (#2 TREATMENTS FOR EVERY SEVERITY LEVEL): n ambulatory care, or in the presence of a person hospitalized for a reason other than COVID-19, but infected with SARS-CoV-2, the decision whether or not to resort to early treatment against COVID-19 is essentially based on the risk of complications. Thus, in order to move towards optimal use of pharmacological treatment options, it is important to gather information on the risk level of complications associated with individuals according to their age, immunity, and comorbidities. The World Health Organization (WHO) recently proposed a stratification according to people's hospitalization level risk, whereby those at moderate to high risk could or should, respectively, receive early treatment against COVID-19. Thus, when the eligibility criteria for early treatment are met, the first-line treatment is nirmatrelvir/ritonavir. In the presence of a contraindication or drug interaction with ritonavir, remdesivir is an alternative option. When a person's condition requires hospitalization for COVID-19, it is important to determine the scale and severity level of the disease, in order to optimize the clinical gain expected from taking the medication. In this respect, the WHO ordinal scale, which associates a category with the need for respiratory or cardiorespiratory assistance, is clinically relevant, especially as all studies on pharmacological treatments are based on it. Thus, standards of care differ according to the severity level of the disease and the category at which the person hospitalized with COVID-19 is categorized. Three drug classes are included in the standard of care in this context: antivirals, anticoagulants, and immunomodulators.(#3 FOLLOW-UP FOCUSED ON PREVENTING FUTURE RESPIRATORY INFECTIONS): Although rare in the current epidemiological context, follow-up by the clinician can sometimes be established in the presence of a more vulnerable patient, such as an immunosuppressed patient. However, the most important thing is to encourage the patient to get vaccinated to prevent future respiratory infections - e.g. influenza, pneumococcus, SARS-CoV-2. (#4 ORGANIZATIONAL ISSUES RAISED BY THE WORK): The discontinuation of the free distribution of antigenic screening tests in pharmacies for the general population, combined with the public's lack of awareness of free access to rapid tests, or to an RT-PCR test, at local service points, poses challenges, particularly for people at risk of complications. To benefit from the advantages associated with early treatment, 5 to 7 days must separate the taking of the medication from the appearance of the first symptoms. Added to this is the lack of awareness of the existence of early treatment among people who could benefit from it, and who are unaware that they should at least consult a clinician in the event of infection due to their health status. CONCLUSION: COVID-19 has a substantial impact on resource utilization, resulting in repeated visits to family practice groups and emergency departments by people with mild COVID-19, or hospital stays, and even intensive care in the most severe cases. Education in the prevention of respiratory infections through vaccination, as well as the behaviours to adopt to prevent the spread of SARS-CoV-2 or other respiratory viruses, are crucial. In addition to these measures, the prevention of COVID-19-related complications in people at moderate to high risk of hospitalization, notably by taking an antiviral, can only be positive for the healthcare system, provided it is done safely. Without replacing clinical judgment, the recommendations published in the optimal use guide should consolidate knowledge and support clinicians in identifying people at significant risk of complications from COVID-19, as well as promoting the optimal use of treatments. The enhancement and harmonization of practice will, however, depend on: • distribution of the optimal use guide; • adherence to and appropriation of the recommendations by the healthcare professionals concerned; • the application of winning conditions to interprofessional work in various care environments, particularly on the front line

Authors' recommendations: At the end of the work and the whole iterative process with members of the Advisory Committee, where scientific data, information, and recommendations drawn from the reviewed literature, contextual items, and the perspective of various consulted stakeholders were triangulated, clinical benchmarks and previous recommendations were either renewed, withdrawn, or modulated, and new information and recommendations were added. The new features at the heart of this report have also been incorporated into the new optimal use guide, which replaces the series of clinical tools on specific treatments produced during the pandemic.

Authors' methods: For this work, the evaluation questions were formulated to cover the population, clinical, and organizational dimensions arising from the INESSS Statement of Principles and Ethical Foundations. In collaboration with a scientific information consultant (librarian), a systematic search of scientific literature published between March 2020 and March 2023 was conducted in more than three bibliographic databases. A manual search of grey literature was also conducted in Spring 2023, consulting, among others, the websites of learned societies specializing in infectious diseases, health technology assessment agencies, and other organizations that published recommendations on COVID-19 during the pandemic. A targeted informational search of this literature was conducted until July 2024. Rapid reviews of the scientific literature on the efficacy and safety of various COVID-19 treatments, conducted by the INESSS between 2020 and 2024, were also considered. For the rapid review of clinical practice guidelines, document selection, information extraction, and methodological quality evaluation were conducted independently by two scientific professionals. Official monographs for drugs approved by Health Canada were consulted, as were ongoing surveillance reports published by government agencies. The data and contextual items gathered were analyzed and synthesized by one professional, then validated by a second. This analysis was conducted to contextualize the practice in Quebec, based in particular on elements of the legislative, regulatory, and organizational context specific to the province, and on the perspective of the various stakeholders consulted. To gather the stakeholders' perspective, an Advisory Committee was set up, made up of clinicians from various specialties and areas of expertise. The perspective of experts and specialists who collaborated with the INESSS during the three years of the pandemic (March 2020 to March 2023) was also taken into consideration. The identification of key clinical benchmarks and the formulation of recommendations were conducted in collaboration with members of the Advisory Committee, based in particular on an evaluation of all the documented evidence. Finally, the overall quality of the work, its acceptability, and applicability were evaluated by external readers specializing in the field of interest, as well as future users who were not involved in the work.

Authors' identified further research: Unless the epidemiological context evolves unfavorably as a result of the arrival of a new variant that is more virulent or resistant to current antivirals, the relevance of updating the recommendations will be evaluated four years from the date of publication of this guide, according to the progress of scientific data and the evolution of clinical practices, and to any significant changes in complementary contextual documents published by the Ministère de la Santé et des Services sociaux (MSSS) or the Institut national de santé publique du Québec (INSPQ), or by the health and social services network, or according to the listing or delisting of drugs.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/usage-optimal-des-traitements-de-la-covid-19.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/usage-optimal-des-traitements-de-la-covid-19.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: Gouvernement du Québec