Corticosteroids as Adjunctive Therapy in the Treatment of Influenza: An Updated Cochrane Systematic Review and Meta-analysis.

OBJECTIVES: Corticosteroids may be beneficial in sepsis, but uncertainty remains over their effects in severe influenza. This systematic review updates the current evidence regarding corticosteroids in the treatment of influenza and examines the effect of dose on outcome. DATA SOURCES: Electronic databases (MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL, and Web of Science) and trial registries were searched to October 2018 for randomized controlled trials, quasi-experimental designs, and observational cohort studies reporting corticosteroid versus no corticosteroid treatment in individuals with influenza. STUDY SELECTION AND DATA EXTRACTION: Two researchers independently assessed studies for inclusion. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomized controlled trials) or Newcastle-Ottawa Scale (observational studies). Where appropriate, we estimated the effect of corticosteroids by random-effects meta-analyses using the generic inverse variance method. Meta-regression analysis was used to assess the association of corticosteroid dose and mortality. DATA SYNTHESIS: We identified 30 eligible studies, all observational apart from one randomized controlled trial. Twenty-one observational studies were included in the meta-analysis of mortality, which suggested an adverse association with corticosteroid therapy (odds ratio, 3.90; 95% CI, 2.31-6.60; 15 studies; adjusted hazard ratio, 1.49; 95% CI, 1.09-2.02; six studies). Risk of bias assessment was consistent with potential confounding by indication. Pooled analysis of seven studies showed increased odds of hospital-acquired infection in people treated with corticosteroids (unadjusted odds ratio, 2.74; 95% CI, 1.51-4.95). Meta-regression of the effect of dose on mortality did not reveal an association, but reported doses of corticosteroids in included studies were high (mostly > 40 mg methylprednisolone [or equivalent] per day). CONCLUSIONS: Corticosteroid treatment in influenza is associated with increased mortality and hospital-acquired infection, but the evidence relates mainly to high corticosteroid doses and is of low quality with potential confounding by indication a major concern.

Co-infection in critically ill patients with COVID-19: an observational cohort study from England.

Introduction. During previous viral pandemics, reported co-infection rates and implicated pathogens have varied. In the 1918 influenza pandemic, a large proportion of severe illness and death was complicated by bacterial co-infection, predominantly Streptococcus pneumoniae and Staphylococcus aureus.Gap statement. A better understanding of the incidence of co-infection in patients with COVID-19 infection and the pathogens involved is necessary for effective antimicrobial stewardship.Aim. To describe the incidence and nature of co-infection in critically ill adults with COVID-19 infection in England.Methodology. A retrospective cohort study of adults with COVID-19 admitted to seven intensive care units (ICUs) in England up to 18 May 2020, was performed. Patients with completed ICU stays were included. The proportion and type of organisms were determined at <48 and >48 h following hospital admission, corresponding to community and hospital-acquired co-infections.Results. Of 254 patients studied (median age 59 years (IQR 49-69); 64.6 % male), 139 clinically significant organisms were identified from 83 (32.7 %) patients. Bacterial co-infections/ co-colonisation were identified within 48 h of admission in 14 (5.5 %) patients; the commonest pathogens were Staphylococcus aureus (four patients) and Streptococcus pneumoniae (two patients). The proportion of pathogens detected increased with duration of ICU stay, consisting largely of Gram-negative bacteria, particularly Klebsiella pneumoniae and Escherichia coli. The co-infection/ co-colonisation rate >48 h after admission was 27/1000 person-days (95 % CI 21.3-34.1). Patients with co-infections/ co-colonisation were more likely to die in ICU (crude OR 1.78,95 % CI 1.03-3.08, P=0.04) compared to those without co-infections/ co-colonisation.Conclusion. We found limited evidence for community-acquired bacterial co-infection in hospitalised adults with COVID-19, but a high rate of Gram-negative infection acquired during ICU stay.

Influenza in long-term care facilities.

Long-term care facility environments and the vulnerability of their residents provide a setting conducive to the rapid spread of influenza virus and other respiratory pathogens. Infections may be introduced by staff, visitors or new or transferred residents, and outbreaks of influenza in such settings can have devastating consequences for individuals, as well as placing extra strain on health services. As the population ages over the coming decades, increased provision of such facilities seems likely. The need for robust infection prevention and control practices will therefore remain of paramount importance if the impact of outbreaks is to be minimised. In this review, we discuss the nature of the problem of influenza in long-term care facilities, and approaches to preventive and control measures, including vaccination of residents and staff, and the use of antiviral drugs for treatment and prophylaxis, based on currently available evidence.

Effectiveness of 2009 pandemic influenza A(H1N1) vaccines: A systematic review and meta-analysis.

BACKGROUND: The clinical effectiveness of monovalent influenza A(H1N1)pdm09 vaccines has not been comprehensively summarised. We undertook a systematic review and meta-analysis to assess vaccine effectiveness (VE) for adjuvanted and unadjuvanted vaccines. METHODS: We searched healthcare databases and grey literature from 11 June 2009 to 12 November 2014. Two researchers independently assessed titles and abstracts to identify studies for full review. Random effects meta-analyses estimated the pooled effect size of vaccination compared to placebo or no vaccination for crude and adjusted odds ratios (OR) to prevent laboratory confirmed influenza illness (LCI) and related hospitalization. VE was calculated as (1-pooled OR)∗100. Narrative synthesis was undertaken where meta-analysis was not possible. RESULTS: We identified 9229 studies of which 38 at moderate risk of bias met protocol eligibility criteria; 23 were suitable for meta-analysis. Pooled adjusted VE against LCI with adjuvanted and unadjuvanted vaccines both reached statistical significance (adjuvanted: VE=80%; 95% confidence interval [CI] 59-90%; unadjuvanted: VE=66%; 95% CI 47-78%); in planned secondary analyses, VE in adults often failed to reach statistical significance and pooled point estimates were lower than observed in children. Overall pooled adjusted VE against hospitalization was 61% (95% CI 14-82%); in planned secondary analyses, adjusted VE attained statistical significance in adults aged 18-64years and children for adjuvanted vaccines. Adjuvanted vaccines were significantly more effective in children compared to adults for both outcomes. CONCLUSIONS: Adjuvanted and unadjuvanted monovalent influenza A(H1N1)pdm09 vaccines were both effective in preventing LCI. Overall, the vaccines were also effective against influenza-related hospitalization. For both outcomes adjuvanted vaccines were more effective in children than in adults.