A living WHO guideline on drugs for covid-19

Abstract

Clinical questionWhat is the role of drug interventions in the treatment and prevention of covid-19?RecommendationsThe first version on this living guidance focuses on corticosteroids. It contains a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19. Corticosteroids are inexpensive and are on the World Health Organisation list of essential medicines.Howthis guideline was created This guideline reflects an innovative collaboration between the WHO and the MAGIC Evidence Ecosystem Foundation, driven by an urgent need for global collaboration to provide trustworthy and living covid-19 guidance. A standing international panel of content experts, patients, clinicians, and methodologists, free from relevant conflicts of interest, produce recommendations for clinical practice. The panel follows standards, methods, processes, and platforms for trustworthy guideline development using the GRADE approach. We apply an individual patient perspective while considering contextual factors (that is, resources, feasibility, acceptability, equity) for countries and healthcare systems.The evidenceA living systematic review and network meta-analysis, supported by a prospective meta-analysis, with data from eight randomised trials (7184 participants) found that systemic corticosteroids probably reduce 28 day mortality in patients with critical covid-19 (moderate certainty evidence; 87 fewer deaths per 1000 patients (95% confidence interval 124 fewer to 41 fewer)), and also in those with severe disease (moderate certainty evidence; 67 fewer deaths per 1000 patients (100 fewer to 27 fewer)). In contrast, systemic corticosteroids may increase the risk of death in patients without severe covid-19 (low certainty evidence; absolute effect estimate 39 more per 1000 patients, (12 fewer to 107 more)). Systemic corticosteroids probably reduce the need for invasive mechanical ventilation, and harms are likely to be minor (indirect evidence).Understanding the recommendationsThe panel made a strong recommendation for use of corticosteroids in severe and critical covid-19 because there is a lower risk of death among people treated with systemic corticosteroids (moderate certainty evidence), and they believe that all or almost all fully informed patients with severe and critical covid-19 would choose this treatment. In contrast, the panel concluded that patients with non-severe covid-19 would decline this treatment because they would be unlikely to benefit and may be harmed. Moreover, taking both a public health and a patient perspective, the panel warned that indiscriminate use of any therapy for covid-19 would potentially rapidly deplete global resources and deprive patients who may benefit from it most as potentially lifesaving therapy.UpdatesThis is a living guideline. Work is under way to evaluate other interventions. New recommendations will be published as updates to this guideline.Readers noteThis is version 1 of the living guideline, published on 4 September (BMJ 2020;370:m3379) version 1. Updates will be labelled as version 2, 3 etc. When citing this article, please cite the version number.SubmittedAugust 28AcceptedAugust 31

Increasing Age, the Existence of Comorbidities, and Corticosteroid Treatment in Combination With Antiviral Therapy Prolongs the Recovery of SARS-COV-2-Infected Patients, Measured as the Conversion From Positive to Negative rtPCR: A 239 Patients' Retrospective Study

“…Dexamethasone is the latest drug touted by experts in the UK as a possible treatment for COVID-19, with evidence suggesting that it can successfully reduce deaths from the virus by up to one-third in critically ill patients (42). According to the latest version of the WHO guidelines for COVID-19, severe and critical COVID-19 patients are recommended to use systemic corticosteroids, while non-severe patients are not recommended to use corticosteroids (43). In the present study, all patients had recovery from COVID-19, and no deaths occurred.…”

Recommendations for the Diagnosis, Prevention, and Control of Coronavirus Disease-19 in Children—The Chinese Perspectives

“…We recommend that corticosteroids not be considered in the early phase of disease as it may compromise the virus clearing and inhibit the host's immunity (5,6,8), in line with the WHO conditional recommendation. Furthermore, drawing from the experience of adult COVID-19 patients' management (109), corticosteroid may be considered in pediatric patients, based on expert opinions, if three of the following four indications are met: x fever of more than 38.5 • C, lasting for at least 3 days; y CRP ≥30 mg/L; z serum ferritin ≥1,000 µg/L; { diffused infiltrative changes documented in both lungs. Presence of these criteria actually indicates that the disease is progressive.…”

“…One should ensure its dosing is pediatric appropriate and usage adjusted in accordance to observed clinical response and drug-sensitive test. For patients highly suspected of bacterial coinfection, antibiotics should be initiated immediately while samples be sent for microbiological identification (5,6,8,109). 7) Traditional Chinese Medicine (TCM): Some recipes have been recommended for adult patients and could be considered by pediatricians who command reasonable knowledge of the respective benefits vs. potential risks or side effects (7).…”

The ten reasons why corticosteroid therapy reduces mortality in severe COVID-19

“…SARS -CoV-2 has an epitope that binds the ACE2 enzyme facilitating entry into host cells, which might influence the function of the HPA axis at level (2). SARS-CoV-2 may have an ACTH-mimic peptide that could act as an agonist or antagonist at the ACTH receptor at level (3). Prolonged glucocorticoid treatment is indicated when cortisol production and/or target tissue sensitivity to cortisol are compromised (Online Supplement for Supplementary References).…”