RESUMO
BackgroundRandomised Evaluation of COVID-19 Therapy (RECOVERY) demonstrated that tocilizumab reduces mortality in hospitalized COVID-19 patients. However, substantial uncertainty remains whether tocilizumabs effect is similar across clinically relevant subgroups. Whether this uncertainty can be resolved with Bayesian methods is unknown. Design, Setting, Participants, and InterventionsRECOVERY was a controlled, open-label, platform UK trial that randomized (1:1) 4116 adults with oxygen saturation <92% on room air or receiving oxygen therapy with C-reactive protein [≥]75 mg/L to either usual care or tocilizumab plus usual care. Main outcome measuresMortality and hospital discharge within 28 days. MethodsUsing Bayesian methods, we combined RECOVERY with evidence-based priors in-corporating previous COVID-19 tocilizumab RCTs. The probability of tocilizumabs benefit for respiratory support and corticosteroid subgroups and sensitivity analyses were performed with different prior distributions and baseline risks. ResultsFor all-cause mortality, the posterior probabilities of decreased deaths with tocilizumab were >99% and 19% in patients using and not using corticosteroids, respectively. In patients on simple oxygen only, non-invasive ventilation and invasive mechanical ventilation, the probabilities of decreased mortality were 96%, >99% and 77%, respectively. The probabilities for a clinically significant mortality reduction, as assessed by an absolute risk difference > 3% (number needed to treat [≤] 33), were 77%, 96%, 56%, respectively. Sensitivity analyses highlighted the uncertainty and lack of conclusive evidence for tocilizumabs effect in patients on invasive mechanical ventilation and those without concurrent corticosteroids. Posterior probabilities of benefit for hospital discharge outcome were high and consistent across most subgroups. ConclusionsIn this Bayesian reanalysis, COVID-19 hospitalized patients exposed to corticosteroids or on non-invasive ventilation have a high probability of a clinically meaningful mortality benefit from tocilizumab. Tocilizumab also likely improves discharge from hospital in most subgroups. Future research should further address if patients on invasive mechanical ventilation can also benefit from tocilizumab.
RESUMO
Rapid and accurate SARS-CoV-2 diagnostic testing is essential for controlling the ongoing COVID-19 pandemic. The current gold standard for COVID-19 diagnosis is real-time RT-PCR detection of SARS-CoV-2 from nasopharyngeal swabs. Low sensitivity, exposure risks to healthcare workers, and global shortages of swabs and personal protective equipment, however, necessitate the validation of new diagnostic approaches. Saliva is a promising candidate for SARS-CoV-2 diagnostics because (1) collection is minimally invasive and can reliably be self-administered and (2) saliva has exhibited comparable sensitivity to nasopharyngeal swabs in detection of other respiratory pathogens, including endemic human coronaviruses, in previous studies. To validate the use of saliva for SARS-CoV-2 detection, we tested nasopharyngeal and saliva samples from confirmed COVID-19 patients and self-collected samples from healthcare workers on COVID-19 wards. When we compared SARS-CoV-2 detection from patient-matched nasopharyngeal and saliva samples, we found that saliva yielded greater detection sensitivity and consistency throughout the course of infection. Furthermore, we report less variability in self-sample collection of saliva. Taken together, our findings demonstrate that saliva is a viable and more sensitive alternative to nasopharyngeal swabs and could enable at-home self-administered sample collection for accurate large-scale SARS-CoV-2 testing.
