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Emerg Infect Dis ; 27(5)2021 05.
Article in English | MEDLINE | ID: covidwho-1200875


Understanding the immune response to Middle East respiratory syndrome coronavirus (MERS-CoV) is crucial for disease prevention and vaccine development. We studied the antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia. MERS-CoV-specific neutralizing antibodies were detected for 6 years postinfection.

Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Animals , Antibody Formation , Camelus , Coronavirus Infections/epidemiology , Humans , Saudi Arabia/epidemiology
N Engl J Med ; 383(17): 1645-1656, 2020 10 22.
Article in English | MEDLINE | ID: covidwho-834967


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 number, NCT02845843.).

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