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Acute Management and Long-Term Survival Among Subjects With Severe Middle East Respiratory Syndrome Coronavirus Pneumonia and ARDS.

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Journal Respiratory care
Year 2016
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This article is included in 1 Broad synthesis Broad syntheses (1 reference) 10 Systematic reviews Systematic reviews (10 references)

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BACKGROUND: Data on the management, clinical course, and outcome of critical patients with Middle East Respiratory Syndrome coronavirus are scarce. We report here our experience and long-term outcome of such patients. METHODS: Subjects intubated for management of ARDS from Middle East Respiratory Syndrome coronavirus pneumonia and ARDS during the April-May 2014 outbreak were included. Their characteristics, ICU course, management, and outcome were evaluated. RESULTS: Fourteen subjects, including 3 health-care workers, met study criteria. Besides 2 health-care workers, all subjects had comorbidities. Predominant symptoms were fever, cough, and dyspnea. The worst median PaO2 /FIO2 ratio of 118 post-intubation was seen on the third day, and median APACHE II score was 27. All subjects received lung-protective ventilation and 1 mg/kg/d methylprednisolone infusion for ARDS. Eleven subjects received ribavirin and peginterferon α-2a. Subjects had a critical ICU course and required neuromuscular blockade (n = 11; 79%), required rescue therapy for respiratory failure (n = 8; 57%), developed shock (n = 10; 71%), and required renal replacement therapy (n = 8; 57%). Declining C-reactive protein levels correlated with clinical improvement despite continued positive real-time polymerase chain reaction results. Nine subjects died in ICU. Five subjects, including 3 health-care workers, were discharged from hospital and were alive after 1 y. CONCLUSIONS: Middle East Respiratory Syndrome coronavirus pneumonia with ARDS has high mortality in subjects with comorbidities. The mainstay of treatment is meticulous ARDS management. Those who survived the acute infection and its complications remained well after 1 y in our study. The role of ribavirin and interferon warrants urgent further evaluation.

Primary study

Unclassified

Middle East Respiratory Syndrome Coronavirus during Pregnancy, Abu Dhabi, United Arab Emirates, 2013.

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Authors Malik A , El Masry KM , Ravi M , Sayed F
Journal Emerging infectious diseases
Year 2016
Links Pubmed DOI PubMed Central

This article is included in 2 Broad syntheses Broad syntheses (2 references) 12 Systematic reviews Systematic reviews (12 references)

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As of June 19, 2015, the World Health Organization had received 1,338 notifications of laboratory-confirmed infection with Middle East respiratory syndrome coronavirus (MERS-CoV). Little is known about the course of or treatment for MERS-CoV in pregnant women. We report a fatal case of MERS-CoV in a pregnant woman administered combination ribavirin-peginterferon-α therapy.

Primary study

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Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia.

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Journal BMC infectious diseases
Year 2016
Links Pubmed DOI PubMed Central

This article is included in 2 Broad syntheses Broad syntheses (2 references) 12 Systematic reviews Systematic reviews (12 references)

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BACKGROUND: Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a poorly understood disease with no known treatments. We describe the clinical features and treatment outcomes of patients with laboratory confirmed MERS-CoV at a regional referral center in the Kingdom of Saudi Arabia. METHODS: In 2014, a retrospective chart review was performed on patients with a laboratory confirmed diagnosis of MERS-CoV to determine clinical and treatment characteristics associated with death. Confounding was evaluated and a multivariate logistic regression was performed to assess the independent effect of treatments administered. RESULTS: Fifty-one patients had an overall mortality of 37 %. Most patients were male (78 %) with a mean age of 54 years. Almost a quarter of the patients were healthcare workers (23.5 %) and 41 % had a known exposure to another person with MERS-CoV. Survival was associated with male gender, working as a healthcare worker, history of hypertension, vomiting on admission, elevated respiratory rate, abnormal lung exam, elevated alanine transaminase (ALT), clearance of MERS-CoV on repeat PCR polymerase chain reaction (PCR) testing, and mycophenolate mofetil treatment. Survival was reduced in the presence of coronary artery disease, hypotension, hypoxemia, CXR (chest X-ray) abnormalities, leukocytosis, creatinine >1 · 5 mg/dL, thrombocytopenia, anemia, and renal failure. In a multivariate analysis of treatments administered, severity of illness was the greatest predictor of reduced survival. CONCLUSIONS: Care for patients with MERS-CoV remains a challenge. In this retrospective cohort, interferon beta and mycophenolate mofetil treatment were predictors of increased survival in the univariate analysis. Severity of illness was the greatest predictor of reduced survival in the multivariate analysis. Larger randomized trials are needed to better evaluate the efficacy of these treatment regimens for MERS-CoV.

Primary study

Unclassified

IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study.

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Journal The Journal of antimicrobial chemotherapy
Year 2015
Links Pubmed DOI PubMed Central

This article is included in 3 Broad syntheses Broad syntheses (3 references) 14 Systematic reviews Systematic reviews (14 references)

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OBJECTIVES: Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant mortality. We examined the utility of plasma MERS-CoV PCR as a prognostic indicator and compared the efficacies of IFN-α2a and IFN-β1a when combined with ribavirin in reducing MERS-CoV-related mortality rates. METHODS: We retrospectively analysed 32 patients with confirmed MERS-CoV infection, admitted between April 2014 and June 2014, by positive respiratory sample RT-PCR. Plasma MERS-CoV RT-PCR was performed at the time of diagnosis for 19 patients. RESULTS: The overall mortality rate was 69% (22/32). Ninety percent (9/10) of patients with positive plasma MERS-CoV PCR died compared with 44% (4/9) of those with negative plasma MERS-CoV PCR. Mortality rate in patients who received IFN-α2a was 85% (11/13) compared with 64% (7/11) in those who received IFN-β1a (P = 0.24). The mortality rate in patients with renal failure (14), including 8 on haemodialysis, was 100%. Age >50 years and diabetes mellitus were found to be significantly associated with mortality (OR = 26.1; 95% CI 3.58-190.76; P = 0.001 and OR = 15.74; 95% CI 2.46-100.67; P = 0.004, respectively). The median duration of viral shedding in patients who recovered was 11 days (range 6-38 days). Absence of fever was noted in 5/32 patients. CONCLUSIONS: Plasma MERS-CoV RT-PCR may serve as an effective tool to predict MERS-CoV-associated mortality. Older age and comorbid conditions may have contributed to the lack of efficacy of IFN-α2a or IFN-β1a with ribavirin in treating MERS-CoV. Absence of fever should not exclude MERS-CoV.

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Ribavirin and interferon-α2b as primary and preventive treatment for Middle East respiratory syndrome coronavirus: a preliminary report of two cases.

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Journal Antiviral therapy
Year 2015
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This article is included in 1 Broad synthesis Broad syntheses (1 reference) 6 Systematic reviews Systematic reviews (6 references)

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Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly recognized transmissible viral infection with high virulence and case fatality rates for which there is no currently defined primary treatment or prophylaxis. Saudi Arabia has the largest reported number of cases so far. Like severe acute respiratory syndrome (SARS), MERS is caused by a coronavirus. Combination therapy with interferon-α2b and ribavirin has been used successfully as primary treatment and prophylaxis in SARS. Because of similarities between the two coronaviruses, treatment with ribavarin and interferon-α2b has been suggested as a potential therapy for MERS-CoV. Studies in animal models of MERS-CoV have shown the combination of ribavirin and interferon-α2b to be effective both as primary treatment and prophylaxis. In this report, we describe for the first time use of this combination as a primary treatment for a patient with MERS-CoV infection and as prophylaxis for his spouse and discuss its possible role.

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Kim et al.

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Primary study

Unclassified

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

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Journal The Lancet. Infectious diseases
Year 2014
Links Pubmed DOI PubMed Central

This article is included in 2 Broad syntheses Broad syntheses (2 references) 12 Systematic reviews Systematic reviews (12 references)

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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 χ(2) and Fischer's 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 × 10(9)/L [SD 3·95] vs 9·88 × 10(9)/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=0·54). 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.

Primary study

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Middle Eastern Respiratory Syndrome Corona Virus (MERS CoV): case reports from a tertiary care hospital in Saudi Arabia.

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Journal Annals of Saudi medicine
Year 2014
Links Pubmed DOI PubMed Central

This article is included in 1 Broad synthesis Broad syntheses (1 reference) 7 Systematic reviews Systematic reviews (7 references)

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BACKGROUND AND OBJECTIVES: Middle Eastern respiratory syndrome caused by novel coronavirus (MERS CoV) has been a major public health challenge since it was first described in 2012 in Saudi Arabia. So far, there is no effective treatment for this serious illness, which features a high mortality rate. We report an initial experience of the use of ribavirin and interferon (IFN)-a2b in the management of MERS CoV at a tertiary care hospital. DESIGN AND SETTINGS: A case series of 6 patients admitted with a confirmed diagnosis of MERS CoV were treated with ribavirin and IFN-a2b in addition to supportive management. The patients' demographics, clinical parameters, and outcomes were recorded. Fifty-four close contacts of these patients were screened for MERS CoV. METHODS: Six patients with MERS CoV infection were included in this study. Four cases featured symptomatic disease, including pneumonia and respiratory failure, while 2 were asymptomatic close contacts of the MERS CoV patients. The MERS CoV infection was confirmed by reverse transcription-polymerase chain reaction detection of the consensus viral RNA targets upstream of the E gene (UPE) and open reading frame (ORF1b) on a sputum sample. The patients' demographics, comorbid conditions, time to diagnosis and initiation of treatment, and clinical outcomes were recorded. RESULTS: Three out of 6 patients who had comorbid conditions died during the study period, while 3 had suc.cessful outcomes. The diagnosis and treatment was delayed by an average of 15 days in those patients who died. Only 2 close contacts out of the 54 screened (3.7%) were positive for MERS CoV. CONCLUSION: Treatment with ribavirin and IFN-a2b may be effective in patients infected with MERS CoV. There appears to be a low infectivity rate among close contacts of MERS CoV patients.

Primary study

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Distinct immune response in two MERS-CoV-infected patients: can we go from bench to bedside?

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Journal PloS one
Year 2014
Links Pubmed DOI PubMed Central

This article is included in 2 Broad syntheses Broad syntheses (2 references)

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One year after the occurrence of the first case of infection by the Middle East Respiratory Syndrome coronavirus (MERS-CoV) there is no clear consensus on the best treatment to propose. The World Health Organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in MERS-CoV infection. We compared innate and adaptive immune responses of two patients infected with MERS-CoV to understand the underlying mechanisms involved in the response and propose potential therapeutic approaches. Broncho-alveolar lavage (BAL) of the first week and sera of the first month from the two patients were used in this study. Quantitative polymerase chain reaction (qRTPCR) was performed after extraction of RNA from BAL cells of MERS-CoV infected patients and control patients. BAL supernatants and sera were used to assess cytokines and chemokines secretion by enzyme-linked immunosorbent assay. The first patient died rapidly after 3 weeks in the intensive care unit, the second patient still recovers from infection. The patient with a poor outcome (patient 1), compared to patient 2, did not promote type-1 Interferon (IFN), and particularly IFNα, in response to double stranded RNA (dsRNA) from MERS-CoV. The absence of IFNα, known to promote antigen presentation in response to viruses, impairs the development of a robust antiviral adaptive Th-1 immune response. This response is mediated by IL-12 and IFNγ that decreases viral clearance; levels of both of these mediators were decreased in patient 1. Finally, we confirm previous in vitro findings that MERS-CoV can drive IL-17 production in humans. Host recognition of viral dsRNA determines outcome in the early stage of MERS-CoV infection. We highlight the critical role of IFNα in this initial stage to orchestrate a robust immune response and bring substantial arguments for the indication of early IFNα treatment during MERS-CoV infection.

Primary study

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Virological and serological analysis of a recent Middle East respiratory syndrome coronavirus infection case on a triple combination antiviral regimen.

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Journal International journal of antimicrobial agents
Year 2014
Links Pubmed DOI PubMed Central

This article is included in 7 Systematic reviews Systematic reviews (7 references) 1 Broad synthesis Broad syntheses (1 reference)

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Serological, molecular and phylogenetic analyses of a recently imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) in Greece are reported. Although MERS-CoV remained detectable in the respiratory tract secretions of the patient until the fourth week of illness, viraemia was last detected 2 days after initiation of triple combination therapy with pegylated interferon, ribavirin and lopinavir/ritonavir, administered from Day 13 of illness. Phylogenetic analysis of the virus showed close similarity with other human MERS-CoVs from the recent Jeddah outbreak in Saudi Arabia. Immunoglobulin G (IgG) titres peaked 3 weeks after the onset of illness, whilst IgM levels remained constantly elevated during the follow-up period (second to fifth week of illness). Serological testing confirmed by virus neutralisation assay detected an additional case that was a close contact of the patient.