Ali S. Omrani

Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study

Summary Background Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. Methods In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8–10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used χ2 and Fischers exact test to analyse categorical variables and the t test to analyse continuous variables. Findings We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0–8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5·88 × 109/L [SD 3·95] vs 9·88 × 109/L [6·63]; p=0·023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0·004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0·054). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4·32 g/L [SD 2·47] vs 2·14 g/L [1·90]; p=0·002). Interpretation In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended. Funding None.

A family cluster of Middle East Respiratory Syndrome Coronavirus infections related to a likely unrecognized asymptomatic or mild case

Abstract Background Ninety confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) have been reported to the World Health Organization. We report the details of a second family cluster of MERS-CoV infections from Riyadh, Saudi Arabia. Methods We present the clinical, laboratory and epidemiological details of 3 patients from a family cluster of MERS-CoV infections. Results The first patient developed respiratory symptoms and fever 14 days after admission to hospital for an unrelated reason. He died 11 days later with multi-organ failure. Two of his brothers presented later to another hospital with respiratory symptoms and fever. MERS-CoV infection in the latter 2 patients was confirmed by reverse transcriptase polymerase chain reaction testing. All 3 patients had fever, cough, shortness of breath, bilateral infiltrates on chest x-ray, thrombocytopenia, lymphopenia and rises in serum creatinine kinase and alanine transaminase. No hospital or other social contacts are known to have acquired the infection. It appears that the index patient in this cluster acquired MERS-CoV infection whilst in hospital from an unrecognized mild or asymptomatic case. Conclusion MERS-CoV acquisition from unrecognized mild or asymptomatic cases may be a more important contributor to ongoing transmission than previously appreciated.

Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia

Summary Objectives To report the experience with Middle East respiratory syndrome coronavirus (MERS-CoV) infection at a single center in Saudi Arabia. Methods Cases of laboratory-confirmed MERS-CoV occurring from October 1, 2012 to May 31, 2014 were reviewed retrospectively. Information sources included medical files, infection control outbreak investigations, and the preventive medicine database of MERS-CoV-infected patients. Data were collected on clinical and epidemiological aspects and outcomes. Results Seventy consecutive patients were included. Patients were mostly of older age (median 62 years), male (46, 65.7%), and had healthcare acquisition of infection (39, 55.7%). Fever (43, 61.4%), dyspnea (42, 60%), and cough (38, 54.3%) were the most common symptoms. The majority developed pneumonia (63, 90%) and required intensive care (49, 70%). Infection commonly occurred in clusters. Independent risk factors for severe infection requiring intensive care included concomitant infections (odds ratio (OR) 14.13, 95% confidence interval (CI) 1.58–126.09; p =0.018) and low albumin (OR 6.31, 95% CI 1.24–31.90; p =0.026). Mortality was high (42, 60%), and age ≥65 years was associated with increased mortality (OR 4.39, 95% CI 2.13–9.05; p <0.001). Conclusions MERS-CoV can cause severe infection requiring intensive care and has a high mortality. Concomitant infections and low albumin were found to be predictors of severe infection, while age ≥65 years was the only predictor of increased mortality.

Viral Shedding and Antibody Response in 37 Patients With Middle East Respiratory Syndrome Coronavirus Infection

In a study of viral load, shedding, and immune response in 37 cases of Middle East respiratory syndrome coronavirus infection, virus was not eliminated upon development of neutralizing serum antibodies. Vaccination strategies should not be restricted to eliciting neutralizing antibodies.

Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel enzootic betacoronavirus that was first described in September 2012. The clinical spectrum of MERS-CoV infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi-organ failure; overall mortality is around 35.7%. Bats harbour several betacoronaviruses that are closely related to MERS-CoV but more research is needed to establish the relationship between bats and MERS-CoV. The seroprevalence of MERS-CoV antibodies is very high in dromedary camels in Eastern Africa and the Arabian Peninsula. MERS-CoV RNA and viable virus have been isolated from dromedary camels, including some with respiratory symptoms. Furthermore, near-identical strains of MERS-CoV have been isolated from epidemiologically linked humans and camels, confirming inter-transmission, most probably from camels to humans. Though inter-human spread within health care settings is responsible for the majority of reported MERS-CoV cases, the virus is incapable at present of causing sustained human-to-human transmission. Clusters can be readily controlled with implementation of appropriate infection control procedures. Phylogenetic and sequencing data strongly suggest that MERS-CoV originated from bat ancestors after undergoing a recombination event in the spike protein, possibly in dromedary camels in Africa, before its exportation to the Arabian Peninsula along the camel trading routes. MERS-CoV serosurveys are needed to investigate possible unrecognized human infections in Africa. Amongst the important measures to control MERS-CoV spread are strict regulation of camel movement, regular herd screening and isolation of infected camels, use of personal protective equipment by camel handlers and enforcing rules banning all consumption of unpasteurized camel milk and urine.

Middle East respiratory syndrome coronavirus: current situation and travel-associated concerns

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 brought back memories of the occurrence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. More than 1500 MERS-CoV cases were recorded in 42 months with a case fatality rate (CFR) of 40%. Meanwhile, 8000 cases of SARS-CoV were confirmed in six months with a CFR of 10%. The clinical presentation of MERS-CoV ranges from mild and non-specific presentation to progressive and severe pneumonia. No predictive signs or symptoms exist to differentiate MERS-CoV from community-acquired pneumonia in hospitalized patients. An apparent heterogeneity was observed in transmission. Most MERS-CoV cases were secondary to large outbreaks in healthcare settings. These cases were secondary to community-acquired cases, which may also cause family outbreaks. Travel-associated MERS infection remains low. However, the virus exhibited a clear tendency to cause large outbreaks outside the Arabian Peninsula as exemplified by the outbreak in the Republic of Korea. In this review, we summarize the current knowledge about MERS-CoV and highlight travel-related issues.

Physicians' knowledge, perceptions, and attitudes toward antimicrobial prescribing in Riyadh, Saudi Arabia.

Objectives: To assess knowledge, perceptions, and attitudes toward antimicrobial prescribing among physicians practicing in Riyadh, Saudi Arabia. Methods: A questionnaire was developed and distributed to physicians working in hospitals in Riyadh, Saudi Arabia between June and August 2013. The results were analyzed using Stata 12 software. Results: Two hundred and twelve (84.8%) full responses were returned. Most respondents perceived antimicrobial resistance as a significant problem in their daily practice (119, 56.1%) and at a national level (148, 69.8%). Inappropriate empirical therapy (101, 47.6%) and excessive use of antimicrobials in healthcare settings (66, 31.1%) were believed to be the main contributors to increasing bacterial resistance. Respondents favor treating infection rather than colonization (98, 46.2%), and physician education (74, 34.9%) as the most effective interventions to reduce antimicrobial resistance. Many respondents (95, 44.8%) do not feel confident in their knowledge of antimicrobial prescribing. Two-thirds of the respondents (135, 63.7%) have local antimicrobial guidelines, of which 90 (66.7%) felt were useful. Most respondents (160, 75.5%) considered their local infectious diseases service to be very helpful. Conclusion: There are considerable unmet training and education need for physicians in the area of antimicrobial prescribing. Local antimicrobial guidelines need revision to ensure they are more relevant and helpful for medical practitioners.

GeneXpert MTB/RIF Testing in the Management of Patients with Active Tuberculosis; A Real Life Experience from Saudi Arabia

Background GeneXpert MTB/RIF is a real-time PCR assay with established diagnostic performance in pulmonary and extra-pulmonary forms of tuberculosis. The aim of this study was to assess the contribution of GeneXpert MTB/RIF assay to the management of patients with any form of active tuberculosis in a single large tertiary center in Saudi Arabia, with a special focus on the impact on time to start of antituberculous therapy compared with Ziehl-Neelsen (ZN) smears and mycobacterial cultures. Materials and Methods Clinical, radiological and laboratory records for all patients who were commenced on antituberculous therapy between March 2011 and February 2013 were retrospectively reviewed. Results A total of 140 patients were included, 38.6% of which had pulmonary tuberculosis. GeneXpert MTB/RIF was requested for only 39.2% of patients and was the only reason for starting antituberculous therapy for only 12.1%. The median time to a positive GeneXpert MTB/RIF result was 0 days (IQR 3) compared with 0 day (IQR 1) for smear microscopy (P > 0.999) and 22 days (IQR 21) for mycobacterial cultures (P < 0.001). No patients discontinued antituberculous therapy because of a negative GeneXpert MTB/RIF result. Conclusions In a setting wherein physicians are highly experienced in the diagnosis and treatment of tuberculosis, GeneXpert MTB/RIF was remarkably under-utilized and had only a limited impact on decisions related to starting or stopping antituberculous therapy. Cost-effectiveness and clinical utility of routine testing of all smear-negative clinical samples submitted for tuberculosis investigations by GeneXpert MTB/RIF warrant further study.

Mycobacterium riyadhense infections

Mycobacterium riyadhense is a newly described slowly growing, non-tuberculous mycobacterium species. We describe 2 new cases of Mycobacterium riyadhense infections presenting with extra-pulmonary involvement, and reviewed all previously reported cases in the literature. We also describe the spectrum of the disease and explore treatment options based on the experience with the current and previously reported cases.

Therapeutic Options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: How Close Are We?

Over 1100 cases of MERS-CoV have been reported since it was first identified in June 2012. Clinical presentation ranges from asymptomatic or mild illness to rapidly progressive disease with multi-organ failure and high mortality. Treatment has been largely supportive. A large number of compounds have been shown to have significant in vitro inhibitory activity against MERS-CoV. Until recently, macaques were the only suitable animal models for animal studies, hindering further clinical development of MERS-CoV therapy. However, the recent successful development of MERS-CoV infection model in transduced mice offers opportunities to accelerate clinical development of therapeutic agents for MERS-CoV infection. Currently available evidence supports further clinical investigation of interferon-based treatment regimens for patients with MERS-CoV. Combining interferon with mycophenolate and/or high-dose ribavirin appears especially promising. Monoclonal antibodies against various targets within MERS-CoV Spike protein have yielded encouraging in-vitro results. However, their safety and efficacy require confirmation in animal models and exploratory clinical trials.