ABSTRACT
Clinical question What is the role of drug interventions in the treatment and prevention of covid-19? Recommendations The 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. How this 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 evidence A 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 recommendations The 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. Updates This is a living guideline. Work is under way to evaluate other interventions. New recommendations will be published as updates to this guideline. Readers note This 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. Submitted August 28 Accepted August 31Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to.
ABSTRACT
Background. Coronavirus disease 2019 (COVID-19) patients frequently suffer from long-term sequelae, often called 'long COVID' or 'post COVID-19 condition'. Remdesivir, given in early disease, decreases the risk of hospitalization and potentially mortality. No randomized trials have thus far published long-term follow-up data on any COVID-19 drug treatment. We investigated the effects of remdesivir on a range of patient-important outcomes at one year. Methods. Between July 2020 and January 2021, an open-label randomized multicenter trial in Finland recruited 208 adult patients from 11 Finnish hospitals. Patients were randomly assigned (1:1 ratio) to standard of care (SoC)with remdesivir (median duration of remdesivir treatment 5 days) or SoCalone. Primary outcomes were self-reported recovery, exertional dyspnea, fatigue, and quality of life at one year. Secondary outcomes were overall mortality and several potential long-COVID symptoms. Results. At one year, 5 (4.4%) of 114 patients in the remdesivir and 5 (5.3%) of 94 in the SoC group had died (RR 0.82, 95% CI 0.25-2.76;absolute difference: -0.9%, 95% CI -7.9-5.3);181 (92% of survivors) completed the follow-up. Self-reported recovery (fully or largely) occurred in 85% in remdesivir and in 86% in SoC (RR 0.94, 0.47-1.90;absolute difference: -0.9%, 95% CI -11%-10%). Exertional dyspnea occurred in 5% in remdesivir and 8% in SoC (OR 0.61, 95% CI 0.20-1.85;absolute difference -3.3%, 95% CI -12%-4.4%). We found no convincing difference between remdesivir and SoC groups in quality of life or symptom outcomes (p > 0.05 for all). Of the 21 potential long-COVID symptoms, patients often reported moderate or major bother from fatigue (26%), joint pain (22%), persistent respiratory mucus (21%), and problems with memory (19%) and attention/concentration (18%) (Figure). Bother from potential long-COVID symptoms at one year from COVID-19 hospitalization between the standard of care and standard of care plus remdesivir groups. Conclusion. After a one-year follow-up of hospitalized patients (with a very high participation rate), approximately one in four reported substantial bother from fatigue, and one in six reported that they had not recovered well from COVID-19. We found no convincing evidence of a remdesivir effect, but confidence intervals were wide and included possible substantial benefit and substantial harm.