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Background: Severe acute respiratory infection (SARI) is a major cause for hospital admission and associated with high mortality among children worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses and respiratory syncytial virus (RSV) are the most frequently identified pathogens in children with SARI. The duration of care can be affected by the type of infection and patient characteristics. Therefore, the objective of this study was to identify factors affecting the length of hospitalization in children infected with SARS-CoV-2, influenza A and RSV., Methods: We collected data on 713 children with SARI from the medical databases of a university hospital in Hungary. To examine whether there is a difference in the length of hospitalization in children with the SARI Kruskal-Wallis test was performed. To determine the factors that may have an impact on the duration of care a multiple logistic regression analysis was executed., Results: Our results showed that among RSV infected patients the proportions of children requiring intensive care (8.94%), mechanical ventilation (8.94%) and oxygen therapy (13.01%) and suffering from pneumonia (29.27%) were larger than among cases with SARS-CoV-2 and influenza A infection. Considering the age distribution and the duration of care in children with SARI, cases with RSV were significantly younger (p < 0.001) and stayed longer in the hospital (median: 5 days, IQR: 4-7 days, p < 0.001) than those with SARS-CoV-2 and influenza A virus. Multiple logistic regression analysis showed that RSV infection (adjusted odds ratio (aOR): 3.25, 95% confidence interval (CI): 1.43-7.38; p = 0.005), pneumonia (aOR: 3.65, 95% CI: 2.14-6.24; p < 0.001), mechanical ventilation or oxygen therapy (aOR: 3.23, 95% CI: 1.29-8.11; p = 0.012) and underlying illnesses (aOR: 2.39, 95% CI: 1.35-4.23; p = 0.003) significantly increased the odds of hospitalization for more than 4 days., Conclusions: Our research showed that of the viruses causing SARI, RSV had the greatest clinical relevance, contributing to hospital stays of more than 4 days in a large share of paediatric patients below 1 year of age. Our results supply new information on children with SARI, and provide evidence for health policy makers to allocate additional resources to hospitals during SARI epidemics., (© 2024. The Author(s).)

One hundred years ago, an influenza pandemic swept across the globe that coincided with the development of a neurological condition, named "encephalitis lethargica" for the occurrence of its main symptom, the sudden onset of sleepiness that either developed into coma or gradually receded. Between 1917 and 1920, mortality of the flu was >20 million and of encephalitis lethargica approximately 1 million. For lessons to be learned from this pandemic, it makes sense to compare it with the COVID-19 pandemic, which occurred 100 years later. Biomedical progress had enabled testing, vaccinations, and drug therapies accompanied by public health measures such as social distancing, contact tracing, wearing face masks, and frequent hand washing. From todays' perspective, these public health measures are time honored but not sufficiently proven effective, especially when applied in the context of a vaccination strategy. Also, the protective effects of lockdowns of schools, universities, and other institutions and the restrictions on travel and personal visits to hospitals or old-age homes are not precisely known. Preparedness is still a demand for a future pandemic. Clinical trials should determine the comparative effectiveness of such public health measures, especially for their use as a combination strategy with vaccination and individual testing of asymptomatic individuals. It is important for neurologists to realize that during a pandemic the treatment possibilities for acute stroke and other neurological emergencies are reduced, which has previously led to an increase of mortality and suffering. To increase preparedness for a future pandemic, neurologists play an important role, as the case load of acute and chronic neurological patients will be higher as well as the needs for rehabilitation. Finally, new chronic forms of postviral disease will likely be added, as was the case for postencephalitic parkinsonism a century ago and now has occurred as long COVID., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: In addition to the persistence of SARS-CoV-2 infections, those with Influenza A/B and RSV have reappeared in 2022/23. To compare the development of prevalence, clinical outcomes and risk factors, we analysed data of the season 2023/24 from the same region/hospital as for 2022/23., Methods: Patients covering the whole age range with a positive polymerase chain reaction (PCR) test for SARS-CoV-2, Influenza A/B, RSV were included from the internal, neurological and paediatric units of the RoMed hospital Rosenheim, Germany/Bavaria, from August 1st 2023 to 29th February 2024., Results: Of 932 patients included, 912 showed single infections with SARS-CoV-2, Influenza A or RSV (47.9% female, median age 68.0 years; 52.9% SARS-CoV-2, 23.2% Influenza A, 21.8% RSV). Co-infections (2.0%) and Influenza B (0.1%) were negligible. In patients of age ≥ 18 years (n = 628, 68.5% SARS-CoV-2, 26.0% Influenza A, 5.6% RSV), patients with Influenza A were younger compared to SARS-CoV-2 (p < 0.001), with RSV similar to SARS-CoV-2. Heart failure and asthma were the most prevalent comorbidities for RSV, immunosuppression for Influenza A. Admission to Intensive Care Unit (ICU) occurred in 111 patients (17.0% of SARS-CoV-2, 17.2% Influenza A, 28.6% RSV), and 59 patients died (8.8% SARS-CoV-2, 8.6% Influenza A, 20.0% RSV). Low-flow oxygen supplementation and non-invasive ventilation (NIV) were most frequent for RSV (68.6% and 20.0%, respectively), oxygen demand upon admission for Influenza A (39.3%), without differences in high-flow oxygen supply or length of hospital stay. Among patients aged < 18 years (n = 284, 21.4% SARS-CoV-2, 18.0% Influenza A, 57.1% RSV), 15 were admitted to ICU (4.8% SARS-CoV-2, 3.8% Influenza A, 6.0% RSV); none of them died. Oxygen supply via high-flow, low-flow or upon admission was highest for RSV (23.8%, 70.2%, 21.4%, respectively), as well as the length of hospital stay., Conclusion: Between 8/2023 to 2/2024, a large population of patients hospitalized due to respiratory tract infection, showed relative contributions of SARS-CoV-2, Influenza A or RSV similar to those in 2022/23. The findings underline that in both, adults and children, RSV posed a relatively higher clinical risk than Influenza A and SARS-CoV-2, though absolute numbers remained highest for SARS-CoV-2., (© 2024. The Author(s).)

Background: Respiratory Syncytial Virus (RSV) is an important pathogen causing acute respiratory illnesses in adults. RSV infection can lead to severe outcomes, including hospitalizations and even death. Despite the increased recognition of the burden in older adults, immediate post-discharge care needs among adults hospitalized with RSV are not well characterized and have not been compared to other serious medical conditions (such as influenza, acute myocardial infarction (MI), and stroke) for which there have been long-standing disease prevention efforts., Objectives: This study aims to describe the immediate post-discharge care needs among adults hospitalized with RSV in the United States and descriptively compare it to those hospitalized with influenza, acute MI, or stroke., Design: Retrospective observational cohort study., Patients: Adults aged ≥ 18 years, hospitalized with a primary diagnosis of RSV, influenza, acute MI, or stroke from January 01, 2016, to December 31, 2019, were identified from the Premier Healthcare Database using the International Classification of Diseases (ICD-10) codes., Main Measures: Immediate post-discharge care was categorized into three different levels of care based on the discharge dispositions. Descriptive analyses were performed., Key Results: In total, 3,629 RSV, 303,577 influenza, 388,682 acute MI, and 416,750 stroke hospitalizations were identified, the majority occurred among patients aged ≥ 65 years. Professional home care needs were the highest for RSV hospitalizations (19.1%), followed by influenza (17.7%), stroke (15.4%), and acute MI (9.8%). Additionally, institutional care needs immediately following discharge were similar for RSV, influenza, and acute MI hospitalizations (14.2%, 15.8%, and 14.1%, respectively)., Conclusions: Immediate post-discharge care needs among adults hospitalized with RSV, especially in older adults, can be considerable and comparable to influenza and acute MI discharges. With recently approved RSV vaccines, efforts to increase vaccination in older adults are needed to prevent RSV and associated healthcare consequences., (© 2024. The Author(s).)

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have shown anti-inflammatory potential in multiple inflammatory diseases. In the March 2022 issue of the Journal of Extracellular Vesicles, it was shown that EVs from human MSCs can suppress severe acute respiratory distress syndrome, coronavirus 2 (SARS-CoV-2) replication and can mitigate the production and release of infectious virions. We therefore hypothesized that MSC-EVs have an anti-viral effect in SARS-CoV-2 infection in vivo. We extended this question to ask whether also other respiratory viral infections could be treated by MSC-EVs. Adipose stem cell-derived EVs (ASC-EVs) were isolated using tangential flow filtration from conditioned media obtained from a multi-flask cell culture system. The effects of the ASC-EVs were tested  in Vero E6 cells in vitro. ASC-EVs were also given i.v. to SARS-CoV-2 infected Syrian Hamsters, and H1N1 influenza virus infected mice. The ASC-EVs attenuated SARS-CoV-2 virus replication in Vero E6 cells and reduced body weight and signs of lung injury in infected Syrian hamsters. Furthermore, ASC-EVs increased the survival rate of influenza A-infected mice and attenuated signs of lung injury. In summary, this study suggests that ASC-EVs can have beneficial therapeutic effects in models of virus-infection-associated acute lung injury and may potentially be developed to treat lung injury in humans., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Influenza(flu) in pregnancy is associated with higher rates of hospitalization, ICU admission, and death and with increased odds of congenital anomalies and stillbirth, but not preterm birth. Clinical manifestations of flu in pregnancy are the same as nonpregnant patients. Pregnant individuals with flu-like symptoms or flu exposure should be treated with antivirals. Diagnostic testing is not needed. Oseltamivir is the mainstay of treatment(and prophylaxis), and when given within 48 hours of symptom onset, it decreases morbidity and mortality. Influenza is associated with worse maternal, obstetric, and neonatal outcomes. These risks are mitigated by early oseltamivir treatment and maternal vaccination; hence the recommendation for universal vaccination in pregnancy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Severe infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or influenza virus can cause patients to be admitted to intensive care units (ICUs). It is necessary to understand the differences in clinical characteristics and outcomes between these two types of critically ill patients., Methods: We searched Embase, PubMed, and Web of Science for articles and performed a meta-analysis using Stata 14.0 with a random-effects model. This paper was written in strict accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: Thirty-five articles involving 131,692 ICU patients with coronavirus disease 2019 (COVID-19) and 30,286 ICU patients with influenza were included in our meta-analysis. Compared with influenza patients, COVID-19 patients were more likely to be male (odds ratio (OR) = 1.75, 95% CI: 1.54-1.99) and older (standardized mean difference (SMD) = 0.16, 95% CI: 0.03-0.29). In terms of laboratory test results, COVID-19 patients had higher lymphocyte (SMD = 0.38, 95% CI: 0.17-0.59) and platelet counts (SMD = 0.52, 95% CI: 0.29-0.75) but lower creatinine (SMD = -0.29, 95% CI: -0.55-0.03) and procalcitonin levels (SMD = -0.78, 95% CI: -1.11-0.46). Diabetes (SMD = 1.27, 95% CI: 1.08-1.48) and hypertension (SMD = 1.30, 95% CI: 1.05-1.60) were more prevalent in COVID-19 patients, while influenza patients were more likely to have cancer (OR = 0.52, 95% CI: 0.44-0.62), cirrhosis (OR = 0.52, 95% CI: 0.44-0.62), immunodepression (OR = 0.38, 95% CI: 0.25-0.58), and chronic pulmonary diseases (OR = 0.35, 95% CI: 0.24-0.52). We also found that patients with COVID-19 had longer ICU stays (SMD = 0.20, 95% CI: 0.05-0.34), were more likely to develop acute respiratory distress syndrome (OR = 4.90, 95% CI: 2.77-8.64), and had higher mortality (OR = 1.35, 95% CI: 1.17-1.55)., Conclusions: There are some differences in the basic characteristics, comorbidities, laboratory test results and complications between ICU patients with COVID-19 and ICU patients with influenza. Critically ill patients with COVID-19 often require more medical resources and have worse clinical outcomes. PROSPERO Registration Number: CRD42023452238., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Respiratory viruses are increasingly recognized as a cause of community-acquired pneumonia (CAP). The implementation of new diagnostic technologies has facilitated their identification, especially in vulnerable population such as immunocompromised and elderly patients and those with severe cases of pneumonia. In terms of severity and outcomes, viral pneumonia caused by influenza viruses appears similar to that caused by non-influenza viruses. Although several respiratory viruses may cause CAP, antiviral therapy is available only in cases of CAP caused by influenza virus or respiratory syncytial virus. Currently, evidence-based supportive care is key to managing severe viral pneumonia. We discuss the evidence surrounding epidemiology, diagnosis, management, treatment, and prevention of viral pneumonia., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Whether COVID-19-induced acute respiratory distress syndrome (ARDS) should be approached differently in terms of mechanical ventilation therapy compared to other virus-induced ARDS is debatable. Therefore, we aimed to ascertain whether the respiratory mechanical characteristics of COVID-19-induced ARDS differ from those of influenza A induced ARDS, in order to establish a rationale for mechanical ventilation therapy in COVID-19-induced ARDS., Methods: This was a retrospective cohort study comparing patients with COVID-19-induced ARDS and influenza A induced ARDS. We included intensive care unit (ICU) patients with COVID-19 or Influenza A aged ≥ 19, who were diagnosed with ARDS according to the Berlin definition between January 2015 and July 2021. Ventilation parameters for respiratory mechanics were collected at specific times on days one, three, and seven after intubation., Results: The median age of the 87 participants was 71.0 (62.0-78.0) years old, and 63.2% were male. The ratio of partial pressure of oxygen in arterial blood to the fractional of inspiratory oxygen concentration in COVID-19-induced ARDS was lower than that in influenza A induced ARDS during the initial stages of mechanical ventilation (influenza A induced ARDS 216.1 vs. COVID-19-induced ARDS 167.9, p = 0.009, day 1). The positive end expiratory pressure remained consistently higher in the COVID-19 group throughout the follow-up period (7.0 vs. 10.0, p < 0.001, day 1). COVID-19 and influenza A initially showed different directions for peak inspiratory pressure and dynamic compliance; however, after day 3, both groups exhibited similar directions. Dynamic driving pressure exhibited opposite trends between the two groups during mechanical ventilation., Conclusions: Respiratory mechanics show clear differences between COVID-19-induced ARDS and influenza A induced ARDS. Based on these findings, we can consider future treatment strategies for COVID-19-induced ARDS., (© 2024. The Author(s).)

Rationale: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair., Objective: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis., Methods: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms., Results: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms., Conclusion: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections., (© 2024. The Author(s).)

Objectives: This study aimed to assess the healthcare-seeking behaviour and related factors of people with acute respiratory symptoms in the rural areas of central and western China to estimate the disease burden of influenza more accurately., Design: Cross-sectional survey., Settings: Fifty-two communities/villages in the Wanzhou District, Chongqing, China, a rural area in southwest China, from May 2022 to July 2022., Participants: The participants were those who had been living in Wanzhou District continuously for more than 6 months and consented to participate., Outcome Measures: A semistructured questionnaire was used to determine the healthcare-seeking behaviour of participants, and the dichotomous response of 'yes' or 'no' was used to assess whether participants had acute respiratory symptoms and their healthcare-seeking behaviour., Results: Only 50.92% (360 of 707) of the patients with acute respiratory infection visited medical and health institutions for treatment, whereas 49.08% (347 of 707) avoided treatment or opted for self-medication. The primary reason for not seeing a doctor was that patients felt their condition was not serious and visiting a medical facility for treatment was unnecessary. Short distance (87.54%) and reasonable charges (49.48%) were ranked as the most important reasons for choosing treatment at primary medical and health facilities (80.27%). The primary reasons for which patients visited secondary and tertiary hospitals (7.78% and 8.61%, respectively) were that doctors in such facilities were better at diagnosis (57.14%) and at treatment (87.10%)., Conclusion: The findings provided in this study indicated that regular healthcare-seeking behaviour investigations should be conducted. The disease burden of influenza can be calculated more accurately when healthcare-seeking behaviour investigations are combined with surveillance in the hospitals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To develop, evaluate, and explore the use of a pediatric ordinal score as a potential clinical trial outcome metric in children hospitalized with acute hypoxic respiratory failure caused by viral respiratory infections., Design: We modified the World Health Organization Clinical Progression Scale for pediatric patients (CPS-Ped) and assigned CPS-Ped at admission, days 2-4, 7, and 14. We identified predictors of clinical improvement (day 14 CPS-Ped ≤ 2 or a three-point decrease) using competing risks regression and compared clinical improvement to hospital length of stay (LOS) and ventilator-free days. We estimated sample sizes (80% power) to detect a 15% clinical improvement., Setting: North American pediatric hospitals., Patients: Three cohorts of pediatric patients with acute hypoxic respiratory failure receiving intensive care: two influenza (pediatric intensive care influenza [PICFLU], n = 263, 31 sites; PICFLU vaccine effectiveness [PICFLU-VE], n = 143, 17 sites) and one COVID-19 ( n = 237, 47 sites)., Interventions: None., Measurements and Main Results: Invasive mechanical ventilation rates were 71.4%, 32.9%, and 37.1% for PICFLU, PICFLU-VE, and COVID-19 with less than 5% mortality for all three cohorts. Maximum CPS-Ped (0 = home at respiratory baseline to 8 = death) was positively associated with hospital LOS ( p < 0.001, all cohorts). Across the three cohorts, many patients' CPS-Ped worsened after admission (39%, 18%, and 49%), with some patients progressing to invasive mechanical ventilation or death (19%, 11%, and 17%). Despite this, greater than 76% of patients across cohorts clinically improved by day 14. Estimated sample sizes per group using CPS-Ped to detect a percentage increase in clinical improvement were feasible (influenza 15%, n = 142; 10%, n = 225; COVID-19, 15% n = 208) compared with mortality ( n > 21,000, all), and ventilator-free days (influenza 15%, n = 167)., Conclusions: The CPS-Ped can be used to describe the time course of illness and threshold for clinical improvement in hospitalized children and adolescents with acute respiratory failure from viral infections. This outcome measure could feasibly be used in clinical trials to evaluate in-hospital recovery., Competing Interests: Drs. Newhams, Young, Maddux, Hall, Coates, Kong, Nofziger, Cullinmore, Halasa, Schuster, Gertz, Hume, and Randolph’s (contracts 75D30119C05584 and 75D30120C07725) institutions received funding from the U.S. Centers for Disease Control and Prevention (CDC). Drs. Newhams and Randolph’s institutions received funding from the National Institute of Allergy and Infectious Diseases. Drs. Newhams, Nofziger, Cvijanovich, Flori, and Randolph (AI084011 and AI154470) received support for article research from the National Institutes of Health (NIH). Dr. Khemani received funding from Orange Med/Nihon Kohden and Bayer Pharmaceutical. Dr. Marshall’s institution received funding from the Canadian Institutes of Health Research; he received funding from AM-Pharma and Adrenomed. Drs. Maddux, Kong, Nofziger, Cullimore, Cvijanovich, Schuster, Flori, and Hume’s institutions received funding from the NIH. Dr. Hall received funding from Abbvie, Kiadis, and the American Board of Pediatrics. Dr. Coates’ institution received funding from the National Heart, Lung, and Blood Institute (NHLBI), the American Lung Association, the American Thoracic Society, and the Doris Duke Foundation/Walder Foundation; she received funding from Sobi and Triplett Woolf Garretson LLC. Drs. Kong, Nofziger, Cullimore, Gertz, and Hume received support for article research from the CDC. Drs. Thomas and Cvijanovich’s institution received funding from Boston Children’s Hospital. Dr. Thomas received funding from Bayer AG. Dr. Halasa’s institution received funding from Sanofi and Quidel. Dr. Cvijanovich’s institution received funding from the Cincinnati Children’s Hospital Medical Center. Dr. Shuster’s institution received funding from the AAMC; she received funding from the AAP Department of Health and Human Services. Dr. Flori received funding from Nota Laboratories and Lucira Health; she disclosed that they are a commissioner for a Lancet Child Health report and that they worked as an expert for the NIH-funded pediatric acute respiratory distress syndrome Master Protocol development. Drs. Olson and Patel disclosed government work. Dr. Randolph received funding from UpToDate, Inc. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Passive immunotherapies have been used to treat severe respiratory infections for over a century, with convalescent blood products from recovered individuals given to patients with influenza-related pneumonia as long ago as the Spanish flu pandemic. However, passive immunotherapy with convalescent plasma or hyperimmune intravenous immunoglobulin (hIVIG) has not provided unequivocal evidence of a clinical benefit for severe respiratory infections including influenza and COVID-19. Efficacy trials, primarily conducted in late-stage disease, have demonstrated inconsistent efficacy and clinical benefit for hIVIG treatment of severe respiratory infections. To date, most serological analyses of convalescent plasma and hIVIG trial samples have focused on the measurement of neutralizing antibody titres. There is, however, increasing evidence that baseline antibody levels and extra-neutralizing antibody functions influence the outcome of passive immunotherapy in humans. In this perspective, findings from convalescent plasma and hIVIG trials for severe influenza, COVID-19 and respiratory syncytial virus (RSV) will be described. Clinical trial results will be discussed in the context of the potential beneficial and deleterious roles of antibodies with Fc-mediated effector functions, with a focus on natural killer cells and antibody-dependent cellular cytotoxicity. Overall, we postulate that treating respiratory viral infections with hIVIG represents a delicate balance between protection and immunopathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vanderven and Kent.)

Background: Influenza burden varies across seasons, partly due to differences in circulating influenza virus types or subtypes. Using data from the US population-based surveillance system, Influenza Hospitalization Surveillance Network (FluSurv-NET), we aimed to assess the severity of influenza-associated outcomes in individuals hospitalised with laboratory-confirmed influenza virus infections during the 2010-11 to 2018-19 influenza seasons., Methods: To evaluate the association between influenza virus type or subtype causing the infection (influenza A H3N2, A H1N1pdm09, and B viruses) and in-hospital severity outcomes (intensive care unit [ICU] admission, use of mechanical ventilation or extracorporeal membrane oxygenation [ECMO], and death), we used FluSurv-NET to capture data for laboratory-confirmed influenza-associated hospitalisations from the 2010-11 to 2018-19 influenza seasons for individuals of all ages living in select counties in 13 US states. All individuals had to have an influenza virus test within 14 days before or during their hospital stay and an admission date between Oct 1 and April 30 of an influenza season. Exclusion criteria were individuals who did not have a complete chart review; cases from sites that contributed data for three or fewer seasons; hospital-onset cases; cases with unidentified influenza type; cases of multiple influenza virus type or subtype co-infection; or individuals younger than 6 months and ineligible for the influenza vaccine. Logistic regression models adjusted for influenza season, influenza vaccination status, age, and FluSurv-NET site compared odds of in-hospital severity by virus type or subtype. When missing, influenza A subtypes were imputed using chained equations of known subtypes by season., Findings: Data for 122 941 individuals hospitalised with influenza were captured in FluSurv-NET from the 2010-11 to 2018-19 seasons; after exclusions were applied, 107 941 individuals remained and underwent influenza A virus imputation when missing A subtype (43·4%). After imputation, data for 104 969 remained and were included in the final analytic sample. Averaging across imputed datasets, 57·7% (weighted percentage) had influenza A H3N2, 24·6% had influenza A H1N1pdm09, and 17·7% had influenza B virus infections; 16·7% required ICU admission, 6·5% received mechanical ventilation or ECMO, and 3·0% died (95% CIs had a range of less than 0·1% and are not displayed). Individuals with A H1N1pdm09 had higher odds of in-hospital severe outcomes than those with A H3N2: adjusted odds ratios (ORs) for A H1N1pdm09 versus A H3N2 were 1·42 (95% CI 1·32-1·52) for ICU admission; 1·79 (1·60-2·00) for mechanical ventilation or ECMO use; and 1·25 (1·07-1·46) for death. The adjusted ORs for individuals infected with influenza B versus influenza A H3N2 were 1·06 (95% CI 1·01-1·12) for ICU admission, 1·14 (1·05-1·24) for mechanical ventilation or ECMO use, and 1·18 (1·07-1·31) for death., Interpretation: Despite a higher burden of hospitalisations with influenza A H3N2, we found an increased likelihood of in-hospital severe outcomes in individuals hospitalised with influenza A H1N1pdm09 or influenza B virus. Thus, it is important for individuals to receive an annual influenza vaccine and for health-care providers to provide early antiviral treatment for patients with suspected influenza who are at increased risk of severe outcomes, not only when there is high influenza A H3N2 virus circulation but also when influenza A H1N1pdm09 and influenza B viruses are circulating., Funding: The US Centers for Disease Control and Prevention., Competing Interests: Declaration of interests EJA has consulted for Pfizer, Sanofi Pasteur, GlaxoSmithKline (GSK), Janssen, Moderna, and Medscape; serves on a safety monitoring board for Kentucky BioProcessing and Sanofi Pasteur; and serves on a data adjudication board for WCG and ACI Clinical. EJA's institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sanofi Pasteur, Janssen, and Micron, and has also received funding from the US National Institutes of Health to conduct clinical trials of COVID-19 vaccines. ES notes the agency grant funding supporting the data collection for this project, and agency grant funding from the US Centers for Disease Control and Prevention (CDC) to support other epidemiology projects. HKT, WS, NBA, JM, KY-H, RKH, and RL have received CDC grant funding. JH and LL have received grants from the Michigan Department of Health and Human Services. ES reports grants from the Council for State and Territorial Epidemiologists (CSTE) during the conduct of the study and grants from CDC outside the submitted work. AG reports grants from CSTE. All other authors declare no competing interests., (Copyright © 2023 Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To estimate the prevalence of influenza coinfection in COVID-19 patients and investigate its association with severe clinical outcomes., Methods: We systematically searched the Web of Science, PubMed, Scopus, Embase, The Cochrane Library, and CNKI for studies published between January 01, 2020, and May 31, 2023. Meta-analysis was performed to estimate the pooled prevalence of coinfection and the impact on clinical outcomes. Systematic review registered in PROSPERO (CRD42023423113)., Results: A total of 95 studies involving 62,107 COVID-19 patients were included. The pooled prevalence of coinfection with influenza virus was 2.45% (95% confidence interval [CI]: 1.67-3.58%), with a high proportion of influenza A. Compared with mono-infected patients (COVID-19 only), the odds ratio (OR) for severe outcomes (including intensive care unit admission [OR = 2.20, 95% CI: 1.68-2.87, P < 0.001], mechanical ventilation support [OR = 2.73, 95% CI: 1.46-5.10, P = 0.002], and mortality [OR = 2.92, 95% CI: 1.16-7.30, P = 0.022]) was significantly higher among patients coinfected influenza A., Conclusion: Although the prevalence of coinfection is low, coinfected patients are at higher risk of severe outcomes. Enhanced identification of both viruses, as well as individualized treatment protocols for coinfection, are recommended to reduce the occurrence of serious disease outcomes in the future., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Ltd.)

A woman presented to the emergency department for syncope after developing influenza-like symptoms. She tested positive for influenza B. The patient rapidly decompensated into cardiogenic shock over 2 days, requiring aggressive pharmacological therapy and temporary mechanical circulatory support. She made a full recovery. This case highlights the importance of early intervention, urgent transplant evaluation and guideline directed medical therapy in the treatment of fulminant myocarditis secondary to influenza B infection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Samuel M. Brown reports that ReddyPort pays royalties on his invention of an airway device, outside the submitted work. Jonathan D. Casey reports a travel grant from Fisher and Paykel, outside the submitted work. Steven Y. Chang reports consulting fees from PureTech Health and Kiniksa Pharmaceuticals and participation as a data safety monitoring board member for a study at University of California, Los Angeles outside the submitted work. James D. Chappell reports participating as a coinvestigator for a Merck investigator studies program, where he supported surveillance of respiratory syncytial virus infection among hospitalized children in Jordan, outside the submitted work. Manjusha Gaglani reports grants from Abt Associates and Westat, having served as cochair of the Infectious Diseases and Immunization Committee for the Texas Pediatric Society (TPS), and receiving an honorarium for serving as a TPS Project Firstline webinar speaker panelist for Respiratory Virus Review: Clinical Considerations and IPC Guidance, outside the submitted work. Adit A. Ginde reports receiving grants from the National Institutes of Health (NIH), U.S. Department of Defense, AbbVie, and Faron Pharmaceuticals outside the submitted work. Michelle N. Gong reports a grant from NIH outside the submitted work. Carlos G. Grijalva reports grants from NIH, the Agency for Healthcare Research and Quality, Food and Drug Administration, and Syneos Health, and receipt of compensation for participation in an advisory board for Merck outside the submitted work. Natasha Halasa reports receiving grants from Sanofi, Merck, and Quidel outside the submitted work. Akram Khan reports receiving grants from United Therapeutics, Johnson & Johnson, 4D Medical, Eli Lily, Dompe Pharmaceuticals, and GSK outside the submitted work. Adam S. Lauring reports receiving grants from FluLab, NIH/National Institute of Allergy and Infectious Diseases, and Burroughs Wellcome Fund and fees from Sanofi and Roche for consulting on oseltamivir and baloxavir respectively, outside the submitted work. Emily T. Martin reports a grant from Merck outside the submitted work. Christopher Mallow reports medical legal consulting outside the submitted work. Ithan D. Peltan reports grants from NIH and Janssen Pharmaceuticals and institutional support from Asahi Kasei Pharma and Regeneron outside the submitted work. Mayur Ramesh reports participating in a nonbranded speaker program supported by AstraZeneca and serving on an advisory board for Moderna outside the submitted work. No other potential conflicts of interest were disclosed.

Background: The COVID-19 pandemic has exposed gaps and areas of need in health care systems. General practitioners (GPs) play a crucial role in the response to COVID-19 and other respiratory infectious diseases (e.g., influenza). Knowing the current flow of these patients and the real needs of GPs is necessary to implement new therapeutic and diagnostic strategies. We sought to learn about the flow of COVID-19 and flu patients in Spanish primary health centers and understand the training needs in both the diagnosis and treatment of these diseases., Methods: A total of 451 regionally representative GPs completed an online survey between January and February 2022., Results: Most of the GPs had available infection containment measures (79%) and access to point-of-care (POC) rapid diagnostic testing (81%) in their centers. The availability of on-the-day diagnostic tests for COVID-19 was higher than that for influenza (80% vs. 20%). Most GPs referred 1 of 10 COVID-19 or flu patients with moderate to severe disease to the emergency department (80% and 90%, respectively). Training/knowledge was considered good regarding diagnostic tests and vaccines (85%) but null or low regarding antivirals (60%) and monoclonal antibodies (80%)., Conclusions: This survey identified the conditions of Spanish GPs in terms of the diagnosis and treatment of COVID-19 and flu patients. Respondents' comments suggested that quite radical system-level adjustments are needed to allow GPs to capitalize on the potential benefits of POC tests for diagnosis, reduction of referrals, and monitoring of these diseases., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: To estimate payments for the treatment of COVID-19 compared with that of influenza or viral pneumonia (IP), from the perspective of the US payer., Study Design: Retrospective cohort analysis., Methods: Patients with COVID-19 during the period from October 1, 2020, to February 1, 2021, or IP during the period from October 1, 2018, to February 1, 2019, in the IBM MarketScan databases were identified. The index was defined as the date of the first COVID-19 or IP diagnosis. Patients with COVID-19 were stratified by severity. Variables for all patients included demographics and comorbidities at the time of index and duration of disease. IP and COVID-19 cohorts were matched using propensity scores, and inflation-adjusted all-cause payments (ACP), and disease-specific payments (DSP) for IP vs COVID-19 were estimated using generalized linear models., Results: Matched cohorts included 6332 Medicare (female, 58.5%; mean [SD] age, 75.3 [7.6] years), and 397,532 commercially insured patients (female, 57.6%; mean [SD] age, 34.7 [16.7] years). ACP and DSP were significantly higher in the COVID-19 cohort vs IP cohort. Payments for severe/critical COVID-19 were significantly greater than those for IP, with adjusted marginal incremental DSP and ACP of $24,852 (95% CI, $21,573-$28,132) and $50,325 (95% CI, $43,932-$56,718), respectively. IP was significantly less expensive than moderate COVID-19 for commercial payers but not Medicare. IP was more expensive than mild COVID-19 for all payers., Conclusions: Payments associated with severe/critical COVID-19 significantly exceeded those associated with IP. For Medicare, IP was more expensive than mild or moderate COVID-19. For commercial payers, IP was less expensive than moderate COVID-19 but more expensive than mild COVID-19.

Influenza virus is a main cause of acute respiratory tract infections (ARTIs) in children. This is the first double-blind, randomized, and controlled clinical trial examining the efficacy of nasal-spraying probiotic LiveSpo Navax, which contains 5 billion of Bacillus subtilis and B. clausii spores in 5 mL, in supporting treatment of influenza viral infection in pediatric patients. We found that the nasal-spraying Bacillus spores significantly shortened the recovery period and overall treatment by 2 days and increased treatment effectiveness by 58% in resolving all ARTIs' symptoms. At day 2, the concentrations of influenza virus and co-infected bacteria were reduced by 417 and 1152 folds. Additionally, the levels of pro-inflammatory cytokines IL-8, TNF-α, and IL-6 in nasopharyngeal samples were reduced by 1.1, 3.7, and 53.9 folds, respectively. Compared to the standard control group, treatment regimen with LiveSpo Navax demonstrated significantly greater effectiveness, resulting in 26-fold reduction in viral load, 65-fold reduction in bacterial concentration, and 1.1-9.5-fold decrease in cytokine levels. Overall, nasal-spraying Bacillus spores can support the symptomatic treatment of influenza virus-induced ARTIs quickly, efficiently and could be used as a cost-effective supportive treatment for respiratory viral infection in general.Clinical trial registration no: NCT05378022 on 17/05/2022., (© 2023. Springer Nature Limited.)

Background: Influenza is a seasonal acute respiratory tract infection with different strains in circulation at different time periods with varying spectrum of clinical presentation., Objectives: To study the clinical presentation, morbidity, and mortality patterns associated with different strains of influenza virus, to identify the predominant strains related to hospitalization, and to identify the seasonal trend in hospitalization and risk factors for mortality in children aged 1-59 months hospitalized with influenza., Materials and Methods: The records of children hospitalized with influenza were analyzed retrospectively (June 2013 to June 2018). Anonymized data from the Medical Records Department of our Institute, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), were used for the study and waiver of consent was obtained from the Institute Ethics Committee for Human Studies (JIPMER), which also approved the study. The data from the medical records were extracted as per the proforma and entered into Microsoft excel and summary statistics was obtained. Categorical data were expressed as proportion and analyzed using chi square test. Association was tested using odds ratio., Results: Of the 693 children tested for influenza during the study period, 91 were found to be positive for influenza infection and out of which 68 (74.7%) were hospitalized. Infection was seen during both the summer and winter months. The predominant strain being A (H1N1) pdm09 (63.2%). The other strains found were A (H3N2) and Influenza B. The predominant diagnosis was pneumonia. The need for mechanical ventilation was more common with influenza B infection (p = 0.035). No significant risk factors for mortality could be found in our study., Conclusion: An absence of seasonal predilection for the disease was noted with influenza A (H1N1) pdm09 being the predominant strain with influenza B seen as an emerging strain and an important contributor towards morbidity., (© 2023 Wiley Periodicals LLC.)

Purpose: Several studies report decreased hospital admissions for acute exacerbations of COPD (AECOPD) during the COVID-19 pandemic. However, there are no studies that compare AECOPD admissions with admissions for respiratory infections, including COVID-19. This study aimed to examine hospital admission rates for AECOPD, pneumonia, influenza, and COVID-19 among COPD patients, before and during the COVID-19 pandemic., Patients and Methods: We obtained anonymized data on hospital admissions of patients with COPD and a primary diagnosis code for AECOPD, pneumonia, influenza, or COVID-19, from the hospital patient admission register at a large Swedish hospital. The study compared the pandemic period (February 2020-March 2022) to a period before the pandemic (June 2017-January 2020). Sequential phases of the pandemic were evaluated separately. Monthly admission rates were compared using Poisson regression, controlling for admission month., Results: Comparing monthly admission rates during the pandemic with the prepandemic period, incidence rate ratios were 0.72 for AECOPD (95% CI 0.67-0.77; p<0.001), 0.56 for pneumonia (95% CI 0.49-0.62; p<0.001), 0.18 for influenza during the winter period (95% CI 0.10-0.30; p<0.001) and 0.79 for total COPD admissions, including COVID-19 (95% CI 0.75-0.84; p<0.001). The study showed significantly lower rate ratios for AECOPD, pneumonia, and total COPD admissions during the first, second, third, and fifth (Omicron) waves. No significant effect on admissions was seen after the withdrawal of restriction measures., Conclusion: There was a significant reduction in the overall rate of hospital admissions among COPD patients for AECOPD, pneumonia, and respiratory viral infections during the pandemic despite the rise in COVID-19 admissions. However, prepandemic admission levels returned in the post-restriction period., Competing Interests: Dr Lowie EGW Vanfleteren reports personal fees from AstraZeneca, GSK, Boehringer, Novartis, Chiesi, Pulmonx, and Resmed, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Andreen et al.)

Background: The severe forms of influenza infection requiring intensive care unit (ICU) admission remain a medical challenge due to its high mortality. New H1N1 strains were hypothesized to increase mortality. The studies below represent a large series focusing on ICU-admitted influenza patients over the last decade with an emphasis on factors related to death., Methods: A retrospective study of patients admitted in ICU for influenza infection over the 2010-2019 period in Réunion Island (a French overseas territory) was conducted. Demographic data, underlying conditions, and therapeutic management were recorded. A univariate analysis was performed to assess factors related to ICU mortality., Results: Three hundred and fifty adult patients were analyzed. Overall mortality was 25.1%. Factors related to higher mortality were found to be patient age >65, cancer history, need for intubation, early intubation within 48 h after admission, invasive mechanical ventilation (MV), acute respiratory distress syndrome (ARDS), vaso-support drugs, extracorporal oxygenation by membrane (ECMO), dialysis, bacterial coinfection, leucopenia, anemia, and thrombopenia. History of asthma and oseltamivir therapy were correlated with a lower mortality. H1N1 did not impact mortality., Conclusion: Patient's underlying conditions influence hospital admission and secondary ICU admission but were not found to impact ICU mortality except in patients age >65, history of cancer, and bacterial coinfections. Pulmonary involvement was often present, required MV, and often evolved toward ARDS. ICU mortality was strongly related to ARDS severity. We recommend rapid ICU admission of patients with influenza-related pneumonia, management of bacterial coinfection, and early administration of oseltamivir., Competing Interests: All the authors declare that they have no conflict of interest., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: We examine differences in posthospitalisation outcomes, and health system resource use, for patients hospitalised with COVID-19 during the UK's first pandemic wave in 2020, and influenza during 2018 and 2019., Methods: This retrospective cohort study used routinely collected primary and secondary care data. Outcomes, measured for 90 days follow-up after discharge were length of stay in hospital, mortality, emergency readmission and primary care activity., Results: The study included 5132 patients admitted to hospital as an emergency, with COVID-19 and influenza cohorts comprising 3799 and 1333 patients respectively. Patients in the COVID-19 cohort were more likely to stay in hospital longer than 10 days (OR 3.91, 95% CI 3.14 to 4.65); and more likely to die in hospital (OR 11.85, 95% CI 8.58 to 16.86) and within 90 days of discharge (OR 7.92, 95% CI 6.20 to 10.25). For those who survived, rates of emergency readmission within 90 days were comparable between COVID-19 and influenza cohorts (OR 1.07, 95% CI 0.89 to 1.29), while primary care activity was greater among the COVID-19 cohort (incidence rate ratio 1.30, 95% CI 1.23 to 1.37)., Conclusions: Patients admitted for COVID-19 were more likely to die, more likely to stay in hospital for over 10 days and interact more with primary care after discharge, than patients admitted for influenza. However, readmission rates were similar for both groups. These findings, while situated in the context of the first wave of COVID-19, with the associated pressures on the health system, can inform health service planning for subsequent waves of COVID-19, and show that patients with COVID-19 interact more with healthcare services as well as having poorer outcomes than those with influenza., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Extracorporeal membrane oxygenation (ECMO) has been used extensively for H1N1 influenza and coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) to improve gas exchange and quickly correct hypoxemia and hypercapnia. This systematic review summarized the evidence on ECMO for the treatment of COVID-19 and influenza-associated ARDS., Research Design and Methods: This is a systematic review and meta-analysis of studies to compare the efficacy and safety of ECMO with conventional mechanical ventilation in adults with COVID-19 and influenza-associated ARDS. The study performed a structured search on PubMed, Embase, Web of Science, Scopus and The Cochrane Library. The primary outcome was hospital mortality., Results: The study included 15 observational studies with 5239 patients with COVID-19 and influenza-associated ARDS. The use of ECMO significantly reduced in-hospital mortality in COVID-19-associated ARDS (OR = 0.40; 95% CI = 0.27-0.58; P  < 0.00001) but did not reduce influenza-related mortality (OR = 1.08; 95% CI = 0.41-2.87; P  = 0.87). Moreover, ECMO treatment meaningfully increased the incidence of bleeding complications (OR = 7.66; 95% CI = 2.47-23.72; P  = 0.0004)., Conclusion: The use of ECMO significantly reduced in-hospital mortality in COVID-19- associated ARDS, which may be related to the advances in ECMO-related techniques and the increased experience of clinicians. However, the incidence of bleeding complications remains high. [Figure: see text].

Background: COVID-19 has led to increased numbers of patients in need of venovenous extracorporeal membrane oxygenation (ECMO) support, but knowledge on management in comparison to acute respiratory distress syndrome (ARDS) of other etiologies is still lacking. We analyzed venovenous ECMO management and survival outcomes in patients with COVID-19 in comparison to influenza ARDS and pulmonary ARDS of other origin. Results: Retrospective analysis of prospective venovenous ECMO registry-based data collection was performed. One hundred consecutive venovenous ECMO patients with severe ARDS were included (41 COVID-19, 24 influenza A, 35 ARDS of other etiologies). Patients with COVID-19 had higher BMI (body mass index), lower SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores, lower C-reactive protein and procalcitonin levels and less vasoactive support at ECMO initiation. Significantly more patients were mechanically ventilated for more than 7 days prior to ECMO initiation in the COVID-19 group, however they were ventilated with lower tidal volumes and more often received additional rescue therapies prior to and on ECMO. COVID-19 patients had significantly more barotrauma and thrombotic events on ECMO. There were no differences in weaning of ECMO, however duration of ECMO runs and ICU length of stay was significantly longer in the COVID-19 group. The leading cause of death in the COVID-19 group was irreversible respiratory failure, while uncontrolled sepsis and multiorgan failure were leading causes in the other 2 groups. All patients who survived ICU treatment were discharged out of hospital, and there were no differences in survival among groups at 180 days. Conclusions: Survival outcomes of venovenous ECMO patients do not differ between COVID-19 and ARDS of other pulmonary etiologies. ARDS guidelines were in greater proportion adhered to in COVID-19 patients, with, however, longer time to ECMO initiation. COVID-19 ARDS seems specific as a more single-organ disease with longer ECMO duration and irreversible respiratory failure as a main cause of ICU mortality.

Serious manifestations of respiratory virus infections such as influenza and coronavirus disease 2019 (COVID-19) are associated with a dysregulated immune response and systemic inflammation. Treating the immunological/inflammatory dysfunction with glucocorticoids, Janus kinase inhibitors, and monoclonal antibodies against the interleukin-6 receptor has significantly reduced the risk of respiratory failure and death in hospitalized patients with severe COVID-19, but the proportion of those requiring invasive mechanical ventilation (IMV) and dying because of respiratory failure remains elevated. Treatment of severe influenza-associated pneumonia and acute respiratory distress syndrome (ARDS) with available immunomodulators and anti-inflammatory compounds is still not recommended. New therapies are therefore needed to reduce the use of IMV and the risk of death in hospitalized patients with rapidly increasing oxygen demand and systemic inflammation who do not respond to the current standard of care. This paper provides a critical assessment of the published clinical trials that have tested the investigational use of intravenously administered allogeneic mesenchymal stem/stromal cells (MSCs) and MSC-derived secretome with putative immunomodulatory/antiinflammatory/regenerative properties as add-on therapy to improve the outcome of these patients. Increased survival rates are reported in 5 of 12 placebo-controlled or open-label comparative trials involving patients with severe and critical COVID-19 and in the only study concerning patients with influenza-associated ARDS. Results are encouraging but inconclusive for the following reasons: small number of patients tested in each trial; differences in concomitant treatments and respiratory support; imbalances between study arms; differences in MSC source, MSC-derived product, dosing and starting time of the investigational therapy; insufficient/inappropriate reporting of clinical data. Solutions are proposed for improving the clinical development plan, with the aim of facilitating regulatory approval of the MSC-based investigational therapy for life-threatening respiratory virus infections in the future. Major issues are the absence of a biomarker predicting responsiveness to MSCs and MSC-derived secretome and the lack of pharmacoeconomic evaluations., (© 2023. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Background: It is unknown that whether frailty is a risk factor of influenza and the hospitalization among older adults, although it has been shown that frailty was associated with poor recovery from the hospitalization among those. We examined the association of frailty with influenza and the hospitalization and the effect by sex among independent older adults., Methods: We used the longitudinal data from the Japan Gerontological Evaluation Study (JAGES), performed in 2016 and 2019 and conducted in 28 municipalities in Japan. The target population comprised 77,103 persons aged ≥ 65 years who did not need assistance from the public long-term care insurance. Primary outcome measures were influenza and hospitalization due to influenza. Frailty was evaluated with the Kihon check list. We estimated the risk of influenza, the hospitalization, those risks by sex, and the interaction for frailty and sex using Poisson regression adjusting for covariates., Results: Frailty was associated with both influenza and the hospitalization among the older adults compared with nonfrail individuals after adjusting for covariates (influenza, frail: risk ratio {RR}: 1.36, 95% confidence interval {95% CI}: 1.20 - 1.53, and prefrail: RR: 1.16, 95% CI: 1.09 - 1.23; the hospitalization, frail: RR: 3.18, 95% CI: 1.84 - 5.57, and prefrail: RR: 2.13, 95% CI: 1.44 - 3.16). Male was associated with the hospitalization, but not associated with influenza compared to female (the hospitalization: RR: 1.70, 95% CI: 1.15 - 2.52 and influenza: RR: 1.01, 95% CI: 0.95 - 1.08). The interaction for frailty and sex was significant neither in influenza nor in the hospitalization., Conclusion: These results suggest that frailty is a risk of influenza and the hospitalization, that risks of the hospitalization are different by sex, but that the sex difference does not cause the effect heterogeneity of frailty on the susceptibility and severity among independent older adults., (© 2023. The Author(s).)

Acute respiratory distress syndrome (ARDS) is one the leading causes of mortality and morbidity in patients with COVID-19 and Influenza, with only small number of studies comparing these two viral illnesses in the setting of ARDS. Given the pathogenic differences in the two viruses, this study shows trends in national hospitalization and outcomes associated with COVID-19- and Influenza-related ARDS. To evaluate and compare the risk factors and rates of the adverse clinical outcomes in patients with COVID-19 associated ARDS (C-ARDS) relative to Influenza-related ARDS (I-ARDS), we utilized the National Inpatient Sample (NIS) database 2020. Our sample includes 106,720 patients hospitalized with either C-ARDS or I-ARDS between January and December 2020, of which 103,845 (97.3%) had C-ARDS and 2875 (2.7%) had I-ARDS. Propensity-matched analysis demonstrated a significantly higher in-hospital mortality (aOR 3.2, 95% CI 2.5-4.2, p < 0.001), longer mean length of stay (18.7 days vs. 14.5 days, p < 0.001), higher likelihood of requiring vasopressors (aOR 1.7, 95% CI 2.5-4.2) and invasive mechanical ventilation (IMV) (aOR 1.6, 95% CI 1.3-2.1) in C-ARDS patients. Our study shows that COVID-19-related ARDS patients had a higher rate of complications, including higher in-hospital mortality and a higher need for vasopressors and invasive mechanical ventilation relative to Influenza-related ARDS; however, it also showed an increased utilization of mechanical circulatory support and non-invasive ventilation in Influenza-related ARDS. It emphasizes the need for early detection and management of COVID-19.

Systemic capillary leak syndrome (SCLS) is a rare and under-recognized disease which is potentially fatal. We report a case of SCLS triggered by influenza A infection associated with fulminant cardiogenic shock, successfully supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Strong clinical suspicion with appropriate supportive treatment can be life-saving for patients with SCLS.

Background: Viral community-acquired pneumonia (CAP) is a potentially serious illness, particularly in adult patients with underlying chronic conditions. In addition to the most recent SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) are considered the most relevant causes of viral CAP., Aims: To describe the clinical features of hospitalised adults admitted for influenza-A/B and RSV pneumonia and analyse, according to aetiology, factors associated with non-invasive ventilation (NIV) failure and in-hospital death (IHD)., Methods: This was a retrospective and multi-centre study of all adults who were admitted for laboratory-confirmed influenza-A/B or RSV pneumonia, during two consecutive winter seasons (October-April 2017-2018 and 2018-2019) in three tertiary hospitals in Portugal, Italy and Cyprus., Results: A total of 356 adults were included in the study. Influenza-A, influenza-B and RSV were deemed to cause pneumonia in 197 (55.3%), 85 (23.9%) and 74 (20.8%) patients, respectively. Patients with both obstructive sleep apnoea or obesity hypoventilation syndrome and influenza-A virus pneumonia showed a higher risk for NIV failure (odds ratio (OR) 4.66; 95% confidence interval (CI) 1.42-15.30). Patients submitted to NIV showed a higher risk for IHD, regardless of comorbidities (influenza-A OR 3.00; 95% CI 1.35-6.65, influenza-B OR 4.52; 95% CI 1.13-18.01, RSV OR 5.61; 95% CI 1.26-24.93)., Conclusion: The increased knowledge of influenza-A/B and RSV pneumonia burden may contribute to a better management of patients with viral CAP., (© 2021 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Objective: The objectives of this study were to determine (1) whether obstetrical patients were more likely to be admitted from the emergency department (ED) for influenza compared with nonpregnant women, and (2) require critical care interventions once admitted., Study Design: Using data from the 2006 to 2011 Nationwide Emergency Department Sample, ED encounters for influenza for women aged 15 to 54 years without underlying chronic medical conditions were identified. Women were categorized as pregnant or nonpregnant using billing codes. Multivariable log linear models were fit to evaluate the relative risk of admission from the ED and the risk of intensive care unit (ICU)-level interventions including mechanical ventilation and central monitoring with pregnancy status as the exposure of interest. Measures of association were described with adjusted risk ratios (aRRs) with 95% confidence intervals (CIs)., Results: We identified 15.9 million ED encounters for influenza of which 4% occurred among pregnant women. Pregnant patients with influenza were nearly three times as likely to be admitted as nonpregnant patients (aRR = 2.99, 95% CI: 2.94, 3.05). Once admitted, obstetric patients were at 72% higher risk of ICU-level interventions (aRR = 1.72, 95% CI: 1.61, 1.84). Of pregnant women admitted from the ED, 9.3% required ICU-level interventions such as mechanical ventilation or central monitoring. Older patients and those with Medicare were also at high risk of admission and ICU-level interventions ( p  < 0.01)., Conclusion: Pregnancy confers three times the risk of admission from the ED for influenza and pregnant women are significantly more likely to require ICU-level medical interventions compared with women of similar age. These findings confirm the significant disease burden from influenza in the obstetric population and the public health importance of reducing infection risk., Key Points: · Pregnancy confers three times the risk of admission from the ED for influenza.. · Pregnant women admitted with influenza are significantly more likely to require ICU-level care.. · Influenza represents a significant disease burden in the obstetric population., Competing Interests: M.D. has had a leadership role in American College of Obstetricians and Gynecologists' (ACOG) II's Safe Motherhood Initiative which has received unrestricted funding from the Merck for Mothers. The other authors did not report any potential conflicts of interest., (Thieme. All rights reserved.)

Since 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1,500 human infections and the culling of millions of poultry. Despite large-scale poultry vaccination, H7N9 AIVs continue to circulate among poultry in China and pose a threat to human health. Previously, we isolated and generated four monoclonal antibodies (mAbs) derived from humans naturally infected with H7N9 AIV. Here, we investigated the hemagglutinin (HA) epitopes of H7N9 AIV targeted by these mAbs (L3A-44, K9B-122, L4A-14, and L4B-18) using immune escape studies. Our results revealed four key antigenic epitopes at HA amino acid positions 125, 133, 149, and 217. The mutant H7N9 viruses representing escape mutations containing an alanine-to-threonine substitution at residue 125 (A125T), a glycine-to-glutamic acid substitution at residue 133 (G133E), an asparagine-to-aspartic acid substitution at residue 149 (N149D), or a leucine-to-glutamine substitution at residue 217 (L217Q) showed reduced or completely abolished cross-reactivity with the mAbs, as measured by a hemagglutination inhibition (HI) assay. We further assessed the potential risk of these mutants to humans should they emerge following mAb treatment by measuring the impact of these HA mutations on virus fitness and evasion of host adaptive immunity. Here, we showed that the L4A-14 mAb had broad neutralizing capabilities, and its escape mutant N149D had reduced viral stability and human receptor binding and could be neutralized by both postinfection and antigen-induced sera. Therefore, the L4A-14 mAb could be a therapeutic candidate for H7N9 AIV infection in humans and warrants further investigation for therapeutic applications. IMPORTANCE Avian influenza virus (AIV) H7N9 continues to circulate and evolve in birds, posing a credible threat to humans. Antiviral drugs have proven useful for the treatment of severe influenza infections in humans; however, concerns have been raised as antiviral-resistant mutants have emerged. Monoclonal antibodies (mAbs) have been studied for both prophylactic and therapeutic applications in infectious disease control and have demonstrated great potential. For example, mAb treatment has significantly reduced the risk of people developing severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition to the protection efficiency, we should also consider the potential risk of the escape mutants generated by mAb treatment to public health by assessing their viral fitness and potential to compromise host adaptive immunity. Considering these parameters, we assessed four human mAbs derived from humans naturally infected with H7N9 AIV and showed that the mAb L4A-14 displayed potential as a therapeutic candidate.

The COVID-19 pandemic has been at the forefront of medicine over the last few years. Pregnant women are often exposed to infectious agents that can be harmful not only to the mother but also to the foetus. Moreover, changes during pregnancy means that pregnant women have increased vulnerability to viral infections, especially pulmonary infections. Epidemiological studies have shown a link between maternal viral infections and miscarriage, preterm birth as well as congenital defects. With potential poor outcomes for both women and their newborns, having a good understanding of the presentation and management of these viral pulmonary infections is essential. The increased risk of adverse outcomes has been highlighted during the COVID-19, SARS and H1N1 influenza pandemics., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Recent population-based data are limited regarding influenza-associated hospitalizations in US children., Methods: We identified children <18 years hospitalized with laboratory-confirmed influenza during 2010-2019 seasons, through the Centers for Disease Control and Prevention's Influenza Hospitalization Surveillance Network. Adjusted hospitalization and in-hospital mortality rates were calculated, and multivariable logistic regression was conducted to evaluate risk factors for pneumonia, intensive care unit (ICU) admission, mechanical ventilation, and death., Results: Over 9 seasons, adjusted influenza-associated hospitalization incidence rates ranged from 10 to 375 per 100 000 persons each season and were highest among infants <6 months old. Rates decreased with increasing age. The highest in-hospital mortality rates were observed in children <6 months old (0.73 per 100 000 persons). Over time, antiviral treatment significantly increased, from 56% to 85% (P < .001), and influenza vaccination rates increased from 33% to 44% (P = .003). Among the 13 235 hospitalized children, 2676 (20%) were admitted to the ICU, 2262 (17%) had pneumonia, 690 (5%) required mechanical ventilation, and 72 (0.5%) died during hospitalization. Compared with those <6 months of age, hospitalized children ≥13 years old had higher odds of pneumonia (adjusted odds ratio, 2.7 [95% confidence interval, 2.1-3.4], ICU admission (1.6 [1.3-1.9]), mechanical ventilation (1.6 [1.1-2.2]), and death (3.3 [1.2-9.3])., Conclusions: Hospitalization and death rates were greatest in younger children at the population level. Among hospitalized children, however, older children had a higher risk of severe outcomes. Continued efforts to prevent and attenuate influenza in children are needed., Competing Interests: Potential conflicts of interest. K. P. O. reports grants from Foundation for Atlanta Veterans Education and Research (FAVER) during the conduct of the study. K. Y. H. reports receiving grants from the CDC Emerging Infections Program (EIP) and receiving an hororarium for an invited lecture to the Biology Department at Western Connecticut State University regarding coronavirus disease 2019 (COVID-19) surveillance, outside the submitted work. M. L. M. reports grants and support for travel from the CDC EIP, during the conduct of the study. S. K. reports grants from the Michigan Department of Health and Human Services, during the conduct of the study (Council for State and Territorial Epidemiologists federal grant). R. L. reports grants from the CDC EIP cooperative agreement, during the conduct of the study; receiving royalties as coeditor for a book on infectious disease surveillance (donated to the Minnesota Department of Health); and serving as an associate editor for the American Academy of Pediatrics Red Book (proceeds also donated to the Minnesota Department of Health). C. S. reports receiving grants from New Mexico Department of Health, during the conduct of the study. E. A. reports receiving grants from Pfizer, Sanofi Pasteur, MedImmune, PaxVax, GlaxoSmithKline, Merck, Janssen, and Micron and personal fees from Pfizer, Sanofi Pasteur, and Medscape, outside the submitted work. His institution has also received funding from the National Institutes of Health to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. He also serves on a safety monitoring board for Kentucky BioProcessing and Sanofi Pasteur. L. B. reports receiving grants from the Council for State and Territorial Epidemiologists and the CDC, outside the submitted work (recipient of Epidemiology and Laboratory Capacity and Immunizations and Vaccines for Children grant funding from the CDC to support vaccine preventable disease epidemiology staffing). A. T. reports receiving grants from the CDC EIP cooperative agreement, during the conduct of the study. H. K. T. reports receiving grants from the CDC, during the conduct of the study. W. S. reports grants from the CDC EIP cooperative agreement, during the conduct of the study, and personal fees from VBI Vaccines, outside the submitted work. I. R. reports that her institution has received grants through the Influenza Hospitalization-Based Surveillance Project. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Influenza is a common disease. If it is not treated in time, it may induce related chronic respiratory diseases and seriously endanger people's health. Porridge, as a food of the East, has been recorded by doctors of all ages to treat influenza with porridge. However, due to insufficient research, there is a certain controversy about porridge in the treatment of influenza. We therefore plan to conduct a systematic review and meta-analysis to collect data from all published studies on this issue in order to obtain reliable evidence., Method and Analysis: We will search for relevant trials in various databases published by December 2022. To study the efficacy and safety of a RCT of porridge in the treatment of influenza. Standardized data tables will be used to complete data search and extraction in duplicate. All differences will be resolved by consensus. The main result was to observe the symptom score of influenza patients, and the secondary results included body temperature, nasal secretions, nasal resistance and viral culture titers in the nasal secretions. Data synthesis and statistical analysis will be performed for each outcome with Stata V.14.0., Results: Our study will be a systematic review and meta-analysis to evaluate the efficacy and safety of porridge in the treatment of influenza., Conclusion: The conclusion of this study has a certain reference value for the clinical use of porridge in the treatment of influenza., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To compare the characteristics and outcomes of critically ill patients admitted to the intensive care unit (ICU) due to COVID-19 or influenza- associated pneumonia., Patients and Methods: We conducted a two-center retrospective study on patients admitted to the ICU due to either COVID-19 associated pneumonia (CAP) or influenza-associated pneumonia (IAP). Baseline characteristics, therapy during hospitalization and clinical outcomes were assessed., Results: Our study included 86 patients admitted to the ICU. Twenty-four patients (28%) had IAP and 62 patients (72%) had CAP. Those with IAP had more comorbidities of cardiac disease (p=0.005) and chronic obstructive lung disease (p=0.03) compared to those with CAP. Non-invasive ventilation was used significantly more in patients with IAP (p=0.001). The use of neuromuscular blockade was significantly higher in CAP patients (p=0.001). CAP patients had less favourable ventilation parameters. PEEP was significantly higher in those with CAP on the first day of admission (p=0.002). There was no difference in mortality (p=0.61) between the groups., Conclusions: Patients admission to the ICU with CAP had less comorbidity than those with IAP. Patients with CAP had poorer ventilatory parameters patterns, requiring more aggressive ventilation and ECMO support. The overall mortality did not differ significantly between the groups.

Introduction: The COVID-19 pandemic has emerged as a global health problem, associated with high morbidity and mortality rates. The aim of this study was to compare the outcomes of hospitalized patients with COVID-19 or with seasonal influenza in a teaching hospital in Belgium., Methods: In this retrospective, single-center cohort study, 1384 patients with COVID-19 and 226 patients with influenza were matched using a propensity score with a ratio of 3:1. Primary outcomes included admission to intensive care unit (ICU), intubation rates, hospital length of stay, readmissions within 30 days and in-hospital mortality. Secondary outcomes included pulmonary bacterial superinfection, cardiovascular complications and ECMO., Results: Based on the analysis of the matched sample, patients with influenza had an increased risk of readmission within 30 days (Risk Difference (RD): 0.07, 95% CI: 0.03 to 0.11) and admission to intensive care unit (RD: 0.09, 95% CI: 0.03 to 0.15) compared with those with COVID-19. Patients with influenza had also more pulmonary bacterial superinfections (46.2% vs 7.4%) and more cardiovascular complications (32% vs 3.9%) than patients with COVID-19.However, a two-fold increased risk of mortality (RD: -0.10, 95% CI: 0.15 to -0.05) was observed in COVID-19 compared to influenza. ECMO was also more required among the COVID-19 patients who died than among influenza patients (5% vs 0%)., Conclusions: COVID-19 is associated with a higher in-hospital mortality compared to influenza infection, despite a high rate of ICU admission in the influenza group. These findings highlighted that the severity of hospitalized patients with influenza should not be underestimated., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Evidence suggests that older people aged ≥65 years and those aged 60-64 years with chronic medical conditions are at higher risk of developing severe complications due to influenza virus infection when compared with young, healthy adults. Although seasonal influenza is monitored through a nationwide passive surveillance in Japan, influenza related outcomes and medical resource consumption have not been fully documented. This retrospective database study aimed to describe the epidemiological and clinical characteristics of medically attended influenza cases aged ≥60 years and the associated medical resource consumption in Japan. We used clinically diagnosed influenza (CDI) based on the international classification of disease codes, and laboratory-confirmed influenza (LCI) based on influenza test results, to identify the patient population during a total of nine seasons (2010/2011 to 2018/2019). A total of 372,356 CDI and 31,122 LCI cases were identified from 77 medical institutions. The highest numbers of medically-attended influenza episodes were in patients aged 65-74 years and 75-84 years. On average, across seasons, 5.9% of all-cause hospitalizations were attributable to CDI and 0.4% were LCI. Influenza viruses type A and B co-circulated annually in varying degree of intensity and were associated with similar level of complications, including cardiovascular-related. Oxygen therapy increased with age; by contrast, mechanical ventilation, dialysis, blood transfusion, and intensive care unit admission were higher in the younger groups. In-hospital mortality for inpatients aged ≥ 85 years with CDI and LCI were 18.6% and 15.5%, respectively. Considering the burden associated with medically-attended influenza in this population, influenza prevention, laboratory confirmation and clinical management should be emphasized by general practicians and specialists like cardiologists to protect this aging population., Competing Interests: SC, JN and YH are employed by and hold stocks of Sanofi, a company which produces influenza vaccines.　KH reports personal fees from Otsuka Pharmaceutical, Bayer Yakuhin, Ltd., Daiichi-Sankyo Company, Limited., Sumitomo Dainippon Pharma Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K. YO has received personal fees from Cando, Inc., the Japan Medical Data Center, the Japan Medical Research Institute Co., Ltd, Ohara HealthCare Foundation, Merck & Co., Inc., and Otsuka Pharmaceutical Co., Ltd. This does not alter our adherence to PLOS ONE policies.

The use of complementary and integrative medicine has increased . It is estimated that one-third of the population of the United States uses some form of alternative medicine. Physicians should consider integrative medicine therapies . Alternative medical therapies for the common cold and influenza include herbal supplements, dietary supplements, diet, and other adjunct therapies. However, it is important to research and study these therapies. Therefore, communication with patients and other health care providers is important. This will ensure effective and positive patient care experiences. Further randomized clinical trials are necessary to further establish the role of various alternative options., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Emerging respiratory viruses are major health threats due to their potential to cause massive outbreaks. Over the past 2 years, the coronavirus disease 2019 (COVID-19) pandemic has caused millions of cases of severe infection and deaths worldwide. Although natural and vaccine-induced protective immune mechanisms against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been increasingly identified, the factors that determine morbimortality are less clear. Comparing the immune signatures of COVID-19 and other severe respiratory infections such as the pandemic influenza might help dissipate current controversies about the origin of their severe manifestations. As such, identifying homologies in the immunopathology of both diseases could provide targets for immunotherapy directed to block shared pathogenic mechanisms. Meanwhile, finding unique characteristics that differentiate each infection could shed light on specific immune alterations exploitable for diagnostic and individualized therapeutics for each case. In this study, we summarize immunopathological aspects of COVID-19 and pandemic influenza from the perspective of cytokine storms as the driving force underlying morbidity. Thereby, we analyze similarities and differences in the cytokine profiles of both infections, aiming to bring forward those molecules more attractive for translational medicine and drug development.

Narcolepsy is a life-long sleep disorder with two distinct subtypes, narcolepsy type I and narcolepsy type II. It is now well recognized that the loss of hypocretin neurons underlies the pathogenesis of narcolepsy type I, however, the pathogenesis of narcolepsy type II is currently unknown. Both genetic and environmental factors play an important role in the pathogenesis of narcolepsy. There is increasing evidence that autoimmune processes may play a critical role in the loss of hypocretin neurons. Infections especially streptococcus and influenza have been proposed as a potential trigger for the autoimmune-mediated mechanism. Several recent studies have shown increased cases of pediatric narcolepsy following the 2009 H1N1 pandemic. The increased cases in Europe seem to be related to a specific type of H1N1 influenza vaccination (Pandemrix), while the increased cases in China are related to influenza infection. Children with narcolepsy can have an unusual presentation at disease onset including complex motor movements which may lead to delayed diagnosis. All classic narcolepsy tetrads are present in only a small proportion of children. The diagnosis of narcolepsy is confirmed by either obtaining cerebrospinal fluid hypocretin or overnight sleep study with the multiple sleep latency test (MSLT). There are limitations of using MSLT in young children such that a negative MSLT test cannot exclude narcolepsy. HLA markers have limited utility in narcolepsy, but it may be useful in young children with clinical suspicion of narcolepsy. For management, both pharmacologic and non-pharmacologic treatments are important in the management of narcolepsy. Pharmacotherapy is primarily aimed to address excessive daytime sleepiness and REM-related symptoms such as cataplexy. In addition to pharmacotherapy, routine screening of behavioral and psychosocial issues is warranted to identify patients who would benefit from bio-behavior intervention., (© 2021 Wiley Periodicals LLC.)

Objective: To analyze the survival rates of patients with COVID-19 supported with extracorporeal membrane oxygenation (ECMO) and compare the survival rates of patients with COVID-19 supported with ECMO to patients with influenza supported with ECMO., Design: A systematic review and meta-analysis to assess the impact of ECMO as supportive therapy of COVID-19., Setting: The authors performed a search through the Cochrane, EMBASE, and MEDLINE/PubMed databases from inception to February 19, 2021, for studies reporting hospitalized patients with COVID-19 managed with ECMO., Participants: A total of 134 studies were selected, including 6 eligible for the comparative meta-analysis of COVID-19 versus influenza., Interventions: The authors pooled the risk ratio and random effects model., Measurements and Main Results: The primary endpoint was the overall mortality of patients with COVID-19 receiving ECMO. Of the total number of 58,472 patients with COVID-19 reported, ECMO was used in 4,044 patients. The analysis suggested an overall in-hospital mortality of 39% (95% CI 0.34-0.43). In the comparative analysis, patients with COVID-19 on ECMO had a higher risk ratio (RR) for mortality when compared to influenza patients on ECMO: 72/164 (44%) v 71/186 (38%) RR 1.34; 95% CI 1.05-1.71; p = 0.03., Conclusions: ECMO could be beneficial in patients with COVID-19, according to the authors' meta-analysis. The reported mortality rate was 39%. This systematic analysis can provide clinical advice in the current era and ongoing pandemic., Competing Interests: Conflict of Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Influenza A virus infection is a contagious acute respiratory infection which mostly evolves in an epidemic form, less frequently as pandemic outbreaks. It can take a severe clinical form that needs to be managed in intensive care unit (ICU). The aim of this study was to describe the epidemiological and clinical aspects of influenza A, then to determine independent predictive factors of ICU mortality in Abderrahmen Mami hospital, Ariana, Tunisia., Methods: It was a single-center study, including all hospitalized patients in intensive care, between November 1st, 2009 and October 31st, 2019, with influenza A virus infection. We recorded demographic, clinical and biological data, evolving features; then multivariate analysis of the predictive factors of ICU mortality was realized., Results: During the study period (10 consecutive seasons), 120 patients having severe Influenza A were admitted (Proportion = 2.5%) from all hospitalized patients, with a median age of 48 years and a gender-ratio of 1.14. Among women, 14 were pregnant. Only 7 patients (5.8%) have had seasonal flu vaccine during the year before ICU admission. The median values of the Simplified Acute Physiology Score II, Acute Physiologic and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment were respectively 26, 10 and 3. Virus strains identified with polymerase chain reaction were H1N1 pdm09 (84.2%) and H3N2 (15.8%). Antiviral therapy was prescribed in 88 (73.3%) patients. A co-infection was recorded in 19 cases: bacterial (n = 17) and aspergillaire (n = 2). An acute respiratory distress syndrome (ARDS) was diagnosed in 82 patients. Non-invasive ventilation (NIV) was conducted for 72 (60%) patients with success in 34 cases. Endotracheal intubation was performed in 59 patients with median duration of invasive mechanical ventilation 8 [3.25-13] days. The most frequent complications were acute kidney injury (n = 50, 41.7%), shock (n = 48, 40%), hospital-acquired infections (n = 46, 38.8%) and thromboembolic events (n = 19, 15.8%). The overall ICU mortality rate was of 31.7% (deceased n = 38). Independent predictive factors of ICU mortality identified were: age above 56 years (OR = 7.417; IC95% [1.474-37.317]; p = 0.015), PaO2/FiO2 ≤ 95 mmHg (OR = 9.078; IC95% [1.636-50.363]; p = 0.012) and lymphocytes count ≤ 1.325 109/L (OR = 10.199; IC95% [1.550-67.101]; p = 0.016)., Conclusion: Influenza A in ICU is not uncommon, even in A(H1N1) dominant seasons; its management is highly demanding. It is responsible for considerable morbi-mortality especially in elderly patients., Competing Interests: The authors have declared that no competing interests exist.

At the beginning of the COVID 19 pandemic, the outcome of patients treated with ECMO was discouraging. Subsequently, it became clear that a certain group of patients may benefit from ECMO treatment. The primary objective of this study was to compare the outcome of ECMO treatment in COVID-19 and influenza patients referred to a tertiary care center. A total of 119 adult patients required ECMO treatment following ARDS secondary to H1N1 (49) and SARS-CoV-2 (70) in the referral ECMO Center based in Zagreb between October 2009 and October 2021. Our study revealed a significantly higher mortality in COVID-19 patients compared to H1N1 influenza when the onset of ARDS was severe enough to require ECMO support. Based on these results and current knowledge, we argue that ECMO treatment for ARDS in COVID-19 patients is more challenging compared to H1N1 influenza patients. Therefore, referral to the most experienced ECMO centers should be considered. Additionally, patient selection and timing for ECMO treatment play a key role in relation to outcome. Mortality rate in COVID-19 patients requiring ECMO treatment may be used as a reference frame for ECMO centers to ensure best possible care and outcome.

Aims: The influenza virus is an infectious disease with acute respiratory tract infections, caused secondary bacterial infections and death. In this study, we aimed to determine which predictors were associated with the need for high-flow nasal cannula oxygen therapy (HFNC) and transition to intensive care for influenza virus and also to compare single viral pathogens with multiple ones., Methods: Inpatients under the age of 5 with influenza virus-related respiratory tract infections between November 2015 and March 2019 were included in the study. Demographic features, comorbidities, symptoms, secondary bacterial infection, need for HFNC and pediatric intensive care unit and respiratory support system, length of hospital stay, polymerase chain reaction tests were recorded., Results: A total of 93 patients were included in the study. It was determined that 53.8% of the cases were male and 84.9% were under the age of 2. Comorbidities were present in 50.5% of the cases. Secondary bacterial pneumonia developed in 56.9% of the cases. Patients with secondary bacterial pneumonia had higher PICU need, HFNC need and hospital stay (p = 0.014, p ≤ 0.001 and p ≤ 0.001, respectively). Patients with comorbidity had longer hospital stays and a higher need for HFNC (p ≤ 0.001 and p = 0.001, respectively)., Conclusions: In this study, it was determined that especially comorbidity and secondary bacterial infection aggravated the clinical treatment of hospitalized patients. Therefore, it was concluded that patients with comorbidity should be followed closely and secondary bacterial pneumonia should be recognized and treated early., (© The Author(s) [2022]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)