Background The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. Methods This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. Results Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; P = .29). Conclusions In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

Substantial overlap exists in the clinical presentation and comorbidities among patients with Middle East respiratory syndrome severe acute respiratory infection from other etiologies; therefore, a high index of suspicion combined with diagnostic testing is essential component of severe acute respiratory infection investigation for at-risk patients. The lack of distinguishing clinical features, the need to rely on real-time reverse transcription polymerase chain reaction from respiratory samples, variability in viral shedding duration, lack of effective therapy, and high mortality represent substantial clinical challenges and help guide ongoing clinical research efforts.

The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment.Trial registrationClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.

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Background Noninvasive ventilation (NIV) has been used in patients with the Middle East respiratory syndrome (MERS) with acute hypoxemic respiratory failure, but the effectiveness of this approach has not been studied. Methods Patients with MERS from 14 Saudi Arabian centers were included in this analysis. Patients who were initially managed with NIV were compared to patients who were managed only with invasive mechanical ventilation (invasive MV). Results Of 302 MERS critically ill patients, NIV was used initially in 105 (35%) patients, whereas 197 (65%) patients were only managed with invasive MV. Patients who were managed with NIV initially had lower baseline SOFA score and less extensive infiltrates on chest radiograph compared with patients managed with invasive MV. The vast majority (92.4%) of patients who were managed initially with NIV required intubation and invasive mechanical ventilation, and were more likely to require inhaled nitric oxide compared to those who were managed initially with invasive MV. ICU and hospital length of stay were similar between NIV patients and invasive MV patients. The use of NIV was not independently associated with 90‐day mortality (propensity score‐adjusted odds ratio 0.61, 95% CI [0.23, 1.60] P = 0.27). Conclusions In patients with MERS and acute hypoxemic respiratory failure, NIV failure was very high. The use of NIV was not associated with improved outcomes.

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BackgroundMiddle East Respiratory Syndrome Coronavirus (MERS-CoV) leads to healthcare-associated transmission to patients and healthcare workers with potentially fatal outcomes.AimWe aimed to describe the clinical course and functional outcomes of critically ill healthcare workers (HCWs) with MERS.MethodsData on HCWs was extracted from a multi-center retrospective cohort study on 330 critically ill patients with MERS admitted between (9/2012–9/2015). Baseline demographics, interventions and outcomes were recorded and compared between survivors and non-survivors. Survivors were approached with questionnaires to elucidate their functional outcomes using Karnofsky Performance Status Scale.FindingsThirty-Two HCWs met the inclusion criteria. Comorbidities were recorded in 34% (11/32) HCW. Death resulted in 8/32 (25%) HCWs including all 5 HCWs with chronic renal impairment at baseline. Non-surviving HCW had lower PaO2/FiO2 ratios 63.5 (57, 116.2) vs 148 (84, 194.3), p = 0.043, and received more ECMO therapy compared to survivors, 9/32 (28%) vs 4/24 (16.7%) respectively (p = 0.02).Thirteen of the surviving (13/24) HCWs responded to the questionnaire. Two HCWs confirmed functional limitations. Median number of days from hospital discharge until the questionnaires were filled was 580 (95% CI 568, 723.5) days.ConclusionApproximately 10% of critically ill patients with MERS were HCWs. Hospital mortality rate was substantial (25%). Patients with chronic renal impairment represented a particularly high-risk group that should receive extra caution during suspected or confirmed MERS cases clinical care assignment and during outbreaks. Long-term repercussions of critical illness due to MERS on HCWs in particular, and patients in general, remain unknown and should be investigated in larger studies.

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