The impact of bacterial and viral co‐infection in severe influenza

Please cite this paper as: Blyth et al. (2013) The impact of bacterial and viral co‐infection in severe influenza. Influenza and Other Respiratory Viruses 7(2) 168–176. Background Many questions remain concerning the burden, risk factors and impact of bacterial and viral co‐infection in patients with pandemic influenza admitted to the intensive care unit (ICU). Objectives To examine the burden, risk factors and impact of bacterial and viral co‐infection in Australian patients with severe influenza. Patients/Methods A cohort study conducted in 14 ICUs was performed. Patients with proven influenza A during the 2009 influenza season were eligible for inclusion. Demographics, risk factors, clinical data, microbiological data, complications and outcomes were collected. Polymerase chain reaction for additional bacterial and viral respiratory pathogens was performed on stored respiratory samples. Results Co‐infection was identified in 23·3–26·9% of patients with severe influenza A infection: viral co‐infection, 3·2–3·4% and bacterial co‐infection, 20·5–24·7%. Staphylococcus aureus was the most frequent bacterial co‐infection followed by Streptococcus pneumoniae and Haemophilus influenzae. Patients with co‐infection were younger [mean difference in age = 8·46 years (95% CI: 0·18–16·74 years)], less likely to have significant co‐morbidities (32·0% versus 66·2%, P = 0·004) and less frequently obese [mean difference in body mass index = 6·86 (95% CI: 1·77–11·96)] compared to those without co‐infection. Conclusions Bacterial or viral co‐infection complicated one in four patients admitted to ICU with severe influenza A infection. Despite the co‐infected patients being younger and with fewer co‐morbidities, no significant difference in outcomes was observed. It is likely that co‐infection contributed to a need for ICU admission in those without other risk factors for severe influenza disease. Empiric antibiotics with staphylococcal activity should be strongly considered in all patients with severe influenza A infection.     

Early use of tocilizumab in patients with severe pneumonia secondary to severe acute respiratory syndrome coronavirus 2 infection and poor prognostic criteria: Impact on mortality rate and intensive care unit admission

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 (IL-6) inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against IL-6, stands as an optional treatment for COVID-19 patients presenting this inflammatory hyper-response.We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have also undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function, and improvement of biochemical and hematological parameters were compared between cohorts.Most patients were men, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough, and dyspnoea. 54.8% of patients from the tocilizumab group needed intubation, while in the control group 85.7% needed it. Treatment with tocilizumab significatively increased IL-6 levels, (554.45; CI 95% 186.69, 1032.93; P < .05) while C-reactive protein mean levels were reduced (–108.19; CI 95% –140.15, –75.33; P < .05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25.0% vs 42.9%, P = .021) and the number of ICU admissions (63.9% vs 100.0%, P = .021). 44.1% of patients treated with tocilizumab showed favorable radiological evolution, when compared with 15.4% of patients from the control group.Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease.     

Relationships between A(H1N1)pdm09 influenza infection and infections with other respiratory viruses

Background

A(H1N1)pdm09, a new influenza pandemic virus emerged in 2009. The A(H1N1)pdm09 infection had several unique characteristics which included rapid transmissibility and high morbidity in obese individuals, pregnant women and individuals suffering from chronic diseases.

Objectives

To study the relationships between A(H1N1)pdm09 influenza infection and infections with other respiratory viruses such as respiratory syncytial virus (RSV), human metapneumo virus (hMPV), adenovirus and seasonal influenza.

Methods

Samples (nasopharyngeal swabs or aspirates) collected between 2007 until 2012 from patients of various ages that were hospitalized due to respiratory virus infections were analyzed for the presence of various respiratory viruses, using qRT-PCR.

Results

In 2009–2010, when the pandemic influenza A(H1N1)pdm09 first appeared, two major infection peaks were noted and individuals of various ages were infected. Following the decline of the A(H1N1)pdm09 virus infection, the percentages of patients infected with adenovirus and hMPV increased, while infection frequency with RSV B and with seasonal influenza virus decreased. Furthermore, RSV infections were delayed and very few percentages of patients were co-infected with more than one virus. Interestingly, the A(H1N1)pdm09 virus lost its dominancy when it reappeared in the winter of 2010–2011, and at this time, only the incidence of RSV infections was affected by the A(H1N1)pdm09 virus.

Conclusions

The A(H1N1)pdm09 virus had distinct effects on other respiratory viruses when it first appeared versus later, when it evolved from being a pandemic to a seasonal virus.     

Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections,and association between respiratory syncytial virus infection risk factors and disease severity

This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study. Over a 6-month period (November 1,1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants.Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age or= 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection.The collected data show that, in Italy, RSV is an important cause of lower respiratory tract infection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease.     

Efficacy of Venner-PneuX endotracheal tube system for prevention of ventilator-associated pneumonia in intensive care units: A protocol for systematic review and meta-analysis

Background:The pathogenic mechanism and prevention of ventilator-associated pneumonia (VAP) are substantially improved over the past several decades, but VAP remains frequently seen among the critical cases. The Venner-PneuX endotracheal tube system (VPXETS) has been proved to perform better than standard endotracheal tubes (SET) in the prevention of VAP in some studies. Therefore, this systematic review is aimed at evaluating the effectiveness of VPXETS in order to prevent VAP.Methods:Electronic databases, including PubMed, WANFANG, CENTRAL, CNKI, EMBASE, and CINAHL, are used to search relevant randomized controlled trials for evaluating the therapeutic effect of VPXETS on preventing VAP from January 2011 to December 2020. To be specific, related studies are selected, data are extracted, risk of bias is assessed, and meta-analysis is conducted in succession.Results:The present review aims to assess the therapeutic effect of VPXETS on preventing VAP in intensive care units (ICUs). Our outcome measures include the incidence and side reaction of VAP.Conclusions:The present review assesses related studies regarding the therapeutic effect of VPXETS on preventing VAP at ICUs.Dissemination and ethics:Our findings in this work are to be disseminated by means of peer-reviewed publication. No ethical approval is required in our review since it uses the published data. Moreover, anonymity is guaranteed during the data analysis process.OSF Registration number:DOI 10.17605/OSF.IO/6BERJ     

Prevalence and seasonality of viral respiratory infections in a temperate climate region: A 24‐year study (1997–2020)

BackgroundFew long‐term reports have been published on the epidemiology of respiratory viruses despite their frequent involvement in extremely common infections. The aim here was to determine the frequency and distribution of respiratory viruses in a temperate climate area (Barcelona, Spain) throughout a 24‐year period.MethodsWe collected data on all respiratory viruses detected from 1997 to 2020 in our institution. Clinical specimens were analyzed mainly by conventional techniques, and molecular techniques were also used.ResultsOf the 59,579 specimens analyzed, 21,382 (35.9%) were positive for at least one virus. The number of positive samples during cold months was significantly higher than in warm months. Respiratory virus infections were detected in patients of all ages, above all in children under 3 years of age, who were most frequently infected with the respiratory syncytial virus, whereas Influenza A virus predominated in the other groups, especially in adults. A clear demographic and seasonal pattern was established for some viruses. Circulation of other respiratory viruses during the FLUAV H1N1pdm09 and SARS‐CoV‐2 pandemics was observed.ConclusionsThis long‐term study provides new knowledge about the prevalence of respiratory viruses in a Mediterranean region. Throughout the study period, the frequency of some viruses remained constant, whereas others varied with the year. A clear demographic and seasonal pattern was established for some viruses. Patients suffering from severe respiratory infections should be examined for a range of respiratory viruses regardless of gender, age, or season.     

重症下呼吸道感染降阶梯治疗的效价分析

目的评价降阶梯治疗（de—escalation therapy，DET）方法在治疗呼吸疾病加强监护病房（respiratory intensive care unit，RICU）重症下呼吸道感染中的地位。方法前瞻性对照研究RICU内重症下呼吸道感染（severe low—airway infection，SLAI）机械通气患者67例，以气管插管机械通气为起始点，分为降阶梯治疗（DET）组29例，非降阶梯治疗（NDET）组38例。分析两组前期使用抗生素的情况、下呼吸道分泌物真菌涂片、双套管保护性毛刷下呼吸道分泌物细菌定量培养、机械通气时间、急性生理学和慢性健康状况评分-Ⅱ（APACHE-Ⅱ评分）、治疗转归、抗生素费用、住院总费用等方面的差异。结果DET组住院时间、机械通气时间、住院总费用分别为（14±8）d、（22±16）d、（52871±54457）元，NDET组为（19±12）d、（32±16）d、（82913±49564）元，两组比较差异有统计学意义（t值分别为2．195、2．449、2．354，P均〈0．05）；DET组抗生素总费用为（7896±4718）元，与NDET组的（8490±5786）元比较，差异无统计学意义（t值为0．449，P〉0．05）。DET组病死率及不适当抗生素治疗（IAT）发生率分别为13．8％和27．6％，与NDET组的36．8％和60．5％比较，差异有统计学意义（X2值分别为4．45、7．18，P均〈0．05）。DET组细菌清除率为65．2％，与NDET组的35．7％比较，差异有统计学意义（x^2值为4．40，P〈0．05）。结论降阶梯治疗可明显降低RICU重症下呼吸道感染患者的病死率，缩短机械通气及住院时间，降低住院总费用。     

The application of bi-level positive airway pressure in patients with severe pneumonia and acute respiratory failure caused by influenza A (H1N1) virus

Objective

To evaluate the effect of noninvasive Bi-level Positive Airway Pressure (BiPAP) ventilation on the severe influenza A virus associated with pneumonia and acute respiratory failure (ARF).

Methods

Based on conventional therapy via face mask using BiPAP ventilator positive airway pressure ventilation in the treatment of severe pneumonia caused by influenza A (H1N1) virus with acute respiratory failure (ARF) in 18 cases, we observed and evaluated the therapeutic effects.

Results

PaO2 and SaO2 before and after treatment were (48.85 ± 12.15)mmHg, (68.56 ± 16.25) mmHg and (80 ± 6)%, (92 ± 5)%, respectively. The results were significantly different (P<0.05) before and after treatment. Endotracheal intubation rate was 25% (6/24) and case-fatality rate was 8.3% (2/24).

Conclusion

BiPAP ventilator airway pressure by face mask ventilation can reduce the rate of endotracheal intubation in the treatment of severe pneumonia caused by influenza A (H1N1) virus in acute respiratory failure. It could be an effective approach in the emergency treatment with clinical value.     

Higher risk for influenza‐associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients

BackgroundInfluenza‐associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality.MethodsWe conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR‐confirmed influenza infection and treatment on intensive‐care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in‐hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation.ResultsOne hundred fifty‐eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non‐IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1–67.2]) and days of mechanical ventilation (OR 1.1 [1.1–1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non‐IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU‐mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3–253.4]), influenza A (OR 3.3 [1.4–7.8]), and higher SAPS II score (OR 1.07 [1.05–1.10]) were independent predictors of poor outcome.InterpretationHigh clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.     

Factors associated with severe illness in pandemic 2009 influenza a (H1N1) infection: implications for triage in primary and secondary care

Pandemic (H1N1) 2009 influenza virus (pH1N1/09) infection spread rapidly around the globe, leading to a phase 6 pandemic level of alert declared in June 2009. The WHO declared the end of the pandemic in August 2010. Although for the majority of infected patients, it manifest as a mild, self-limiting illness, a proportion appeared to follow an adverse clinical course, requiring higher level care and aggressive management strategies. Experience with previous pandemics suggests that H1N1 will continue to circulate for many years. The aim of this review is to evaluate data from published case series reporting patients with pH1N1/09 influenza to identify clinical markers of severe disease. Comorbid illnesses including chronic lung disease, obesity and pregnancy have been shown to confer increased risk of severe infection. Admission vital signs, laboratory investigations and chest radiographic features can guide admitting clinicians to stratify patients’ risk of severe disease, however, the currently available severity scoring tools have only a limited role in risk assessment. Knowledge of high risk parameters remains important for clinicians triaging patients with suspected pH1N1/09 influenza and to inform strategies for future pandemics.     

The effect of music therapy on the anxiety,depression and sleep quality in intensive care unit patients: A protocol for systematic review and meta-analysis

Background:Music therapy serves as a non-pharmacological intervention for a variety of disorders with promising results. However, the effect of music therapy on improving anxiety, depression, and sleep quality in intensive care unit (ICU) patients remains unclear. This meta-analysis aims to evaluate the effect of music therapy on improving anxiety, depression, and sleep quality in ICU patients, thus providing evidences to support music therapy as a novel complementary alternative therapy.Methods:Randomized controlled trials (RCTs) reporting the efficacy of music therapy on improving anxiety, depression and sleep quality in ICU patients published before January 2022 will be searched in online databases, including the PubMed, the Cochrane Library, Web of Science, Embase, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Database, and WanFang Database. Literature screening, data extraction, and evaluation of risk of bias will be independently performed by two investigators. Meta-analysis will be performed using Stata 14.0 software.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion:This study will provide reliable evidence-based evidence for the effect of music therapy on anxiety, depression, and sleep quality in ICU patients.Ethics and dissemination:Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms.OSF Registration number:DOI 10.17605/OSF.IO/EXAZ6.     

The association of D-dimers with mortality,intensive care unit admission or acute respiratory distress syndrome in patients hospitalized with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

AimTo determine if D-dimers are elevated in individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who have adverse clinical outcomes including all-cause mortality, intensive care unit (ICU) admission or acute respiratory distress syndrome (ARDS).MethodsWe conducted a systematic review and meta-analysis of the published literature in PubMed, Embase and Cochrane databases through April 9, 2020 for studies evaluating D-dimer levels in SARS-COV-2 infected patients with and without a composite clinical endpoint, defined as the presence of all-cause of mortality, Intensive care unit (ICU) admission or acute respiratory distress syndrome (ARDS). A total of six studies were included in the meta-analysis.ResultsD-dimers were significantly increased in patients with the composite clinical end point than in those without (SMD, 1.67 ug/ml (95% CI, 0.72-2.62 ug/ml). The SMD of the studies (Tang et al, Zhou et al, Chen et al), which used only mortality as an outcome measure was 2.5 ug/mL (95% CI, 0.62-4.41 ug/ml).ConclusionWe conclude that SARS-CoV-2 infected patients with elevated D-dimers have worse clinical outcomes (all-cause mortality, ICU admission or ARDS) and thus measurement of D-dimers can guide in clinical decision making.