A recent living systematic review and network meta-analysis has analysed drug treatments for COVID-19 (Siemieniuk et al, 2020). The objective was to compare the effects of these treatments, using data sources such as the World Health Organization (WHO) COVID-19 database, which contains a comprehensive multilingual source of global COVID-19 literature, including dates up to 3 December 2020, alongside six Chinese databases up to 12 November 2020.
The study involved randomised clinical trials in which people with suspected, probable or confirmed COVID-19 were allocated at random to drug treatment, standard care or placebo. Pairs of reviewers then independently screened potentially eligible articles. Following duplicate data abstraction, a Bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. The team classified interventions for each outcome into groups from the most to the least beneficial or harmful following GRADE guidance (Siemieniuk et al, 2020).
A total of 85 trials with 41 669 patients met the inclusion criteria as of 21 October 2020. Fifty (58.8%) trials and 25 081 (60.2%) patients were newly selected since the last iteration of this analysis; 43 (50.6%) trials that evaluated treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses and can be sourced from the original study. Compared with standard care, corticosteroids were found to probably reduce death and the need for mechanical ventilation and increase days free from mechanical ventilation.
The researchers found that the impact of remdesivir on mortality, mechanical ventilation, length of hospital stay and duration of symptoms is uncertain, but they agreed it is unlikely to substantially increase adverse effects leading to drug discontinuation. Azithromycin, hydroxychloroquine, lopinavir/ritonavir, interferon-beta and tocilizumab were found to probably not reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was found to be low or very low (Siemieniuk et al, 2020).
The authors pointed out that there is now evidence from several large-scale international trials on remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon beta. Unfortunately, however, the trials showed that none of these interventions had a meaningful effect on any patient-important outcomes. The authors are aware of two other similar efforts to their iteration (Boutron et al, 2020; Juul et al, 2020). Siemieniuk et al (2020) decided to proceed independently in order to make sure that the results could fully inform clinical decision-making for the associated living guidance. They also included a more comprehensive search for the evidence and several differences in analytical methods, which they believe are best suited for this process, and they acknowledged the importance in evaluating the reproducibility and replicability of results from various scientific approaches.
The researchers concluded that corticosteroids are likely to reduce mortality and mechanical ventilation and increase ventilator-free days in patients with severe COVID-19. Whether or not remdesivir has an impact on any outcome, however, remains uncertain. Hydroxychloroquine, lopinavir/ritonavir and interferon-beta may not reduce mortality or mechanical ventilation, and appear unlikely to have any other benefits. The authors reiterated that the effects of most drug interventions are highly uncertain, whereby no definitive evidence exists that other interventions result in important benefits and harms for any outcomes. It will be interesting to witness updates to this living systematic review and analysis, as a growing plethora of evidence is produced in further trials.