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1.
N Engl J Med ; 383(17): 1645-1656, 2020 10 22.
Article in English | MEDLINE | ID: mdl-33026741

ABSTRACT

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).


Subject(s)
Coronavirus Infections/drug therapy , Interferon beta-1b/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Administration, Oral , Adult , Aged , Coronavirus Infections/mortality , Double-Blind Method , Drug Combinations , Drug Therapy, Combination , Female , Hospitalization , Humans , Injections, Subcutaneous , Interferon beta-1b/adverse effects , Kaplan-Meier Estimate , Lopinavir/adverse effects , Male , Middle Aged , Ritonavir/adverse effects , Statistics, Nonparametric , Time-to-Treatment
2.
Cent Eur J Public Health ; 26(2): 87-91, 2018 Jun.
Article in English | MEDLINE | ID: mdl-30102495

ABSTRACT

OBJECTIVE: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a novel coronavirus circulating in the Arabian Peninsula since September 2012. It leads to significant respiratory disease and among patients with co-morbidities is associated with high mortality. This research studied the mortality rate of MERS-CoV among intensive care unit (ICU) patients and the correlation of mortality with different co-morbidities. METHODS: This was a retrospective observational study conducted at the Intensive Care Unit of the King Fahad Hospital, Jeddah, Saudi Arabia. Data was obtained through patient chart review. RESULTS: The total sample consisted of 52 laboratory-confirmed MERS-CoV infection patients. 39 patients died, with a 75% case-fatality rate. Many patients had underlying co-morbidities, including diabetes mellitus (51.9%), hypertension (46.2%), and chronic renal disease (21.2%). CONCLUSIONS: MERS-CoV ICU mortality remains markedly high due to a combination of factors; the disease process of MERS-CoV leads to multiple organ failure, particularly respiratory and renal failure.


Subject(s)
Coronavirus Infections/mortality , Coronavirus Infections/virology , Intensive Care Units/statistics & numerical data , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Saudi Arabia/epidemiology
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