Effects of Heat-Killed Levilactobacillus brevis KB290 in Combination with β-Carotene on Influenza Virus Infection in Healthy Adults: A Randomized Controlled Trial

Influenza, a seasonal acute respiratory disease caused primarily by the influenza virus A or B, manifests with severe symptoms leading to considerable morbidity and mortality and is a major concern worldwide. Therefore, effective preventive measures against it are required. The aim of this trial was to evaluate the preventive effects of heat-killed Levilactobacillus brevis KB290 (KB290) in combination with β-carotene (βC) on influenza virus infections in healthy Japanese subjects aged between 20 and 59 y throughout the winter season. We performed a randomized, double-blind, placebo-controlled, parallel-group trial from 16 December 2019 to 8 March 2020, comparing KB290 + βC beverage with placebo beverage. The primary endpoint was the incidence of influenza based on a doctor’s certificate. The incidence of influenza was not significantly different between the two groups. However, the subgroup analysis showed a significant difference between the two groups (influenza incidence: the KB290 + βC group 1.9%, and the placebo group 3.9%) in the subgroup of subjects aged ˂40 y, but not in the subgroup of subjects aged ≥40 y. The results of this trial suggest that the combination of KB290 and βC might be a possible candidate supplement for protection against the seasonal influenza virus infection in humans aged <40 y, although further clinical studies are needed to confirm the concrete preventive effect of this combination on influenza.

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Phase III Randomized, Double-Blind Study Comparing Single-Dose Intravenous Peramivir with Oral Oseltamivir in Patients with Seasonal Influenza Virus Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00360-11 ◽

2011 ◽

Vol 55 (11) ◽

pp. 5267-5276 ◽

Cited By ~ 73

Author(s):

Shigeru Kohno ◽

Muh-Yong Yen ◽

Hee-Jin Cheong ◽

Nobuo Hirotsu ◽

Tadashi Ishida ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Seasonal Influenza ◽

Influenza Virus Infection ◽

Influenza Viruses ◽

Phase Iii ◽

Controlled Study ◽

Double Blind Study ◽

Double Blind

ABSTRACTAntiviral medications with activity against influenza viruses are important in controlling influenza. We compared intravenous peramivir, a potent neuraminidase inhibitor, with oseltamivir in patients with seasonal influenza virus infection. In a multinational, multicenter, double-blind, double-dummy randomized controlled study, patients aged ≥20 years with influenza A or B virus infection were randomly assigned to receive either a single intravenous infusion of peramivir (300 or 600 mg) or oral administration of oseltamivir (75 mg twice a day [b.i.d.] for 5 days). To demonstrate the noninferiority of peramivir in reducing the time to alleviation of influenza symptoms with hazard model analysis and a noninferiority margin of 0.170, we planned to recruit 1,050 patients in South Korea, Japan, and Taiwan. A total of 1,091 patients (364 receiving 300 mg and 362 receiving 600 mg of peramivir; 365 receiving oseltamivir) were included in the intent-to-treat infected population. The median durations of influenza symptoms were 78.0, 81.0, and 81.8 h in the groups treated with 300 mg of peramivir, 600 mg of peramivir, and oseltamivir, respectively. The hazard ratios of the 300- and 600-mg-peramivir groups compared to the oseltamivir group were 0.946 (97.5% confidence interval [CI], 0.793, 1.129) and 0.970 (97.5% CI, 0.814, 1.157), respectively. Both peramivir groups were noninferior to the oseltamivir group (97.5% CI, <1.170). The overall incidence of adverse drug reactions was significantly lower in the 300-mg-peramivir group, but the incidence of severe reactions in either peramivir group was not different from that in the oseltamivir group. Thus, a single intravenous dose of peramivir may be an alternative to a 5-day oral dose of oseltamivir for patients with seasonal influenza virus infection.

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Influenza A Virus Vaccination: Immunity, Protection, and Recent Advances Toward A Universal Vaccine

Vaccines ◽

10.3390/vaccines8030434 ◽

2020 ◽

Vol 8 (3) ◽

pp. 434 ◽

Cited By ~ 2

Author(s):

Christopher E. Lopez ◽

Kevin L. Legge

Keyword(s):

Immune Response ◽

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Influenza Virus Infection ◽

Influenza Viruses ◽

Antigenic Drift ◽

Influenza Vaccines ◽

Virus Infections ◽

Universal Vaccine

Influenza virus infections represent a serious public health threat and account for significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. Despite being an important countermeasure to combat influenza virus and being highly efficacious when matched to circulating influenza viruses, current preventative strategies of vaccination against influenza virus often provide incomplete protection due the continuous antigenic drift/shift of circulating strains of influenza virus. Prevention and control of influenza virus infection with vaccines is dependent on the host immune response induced by vaccination and the various vaccine platforms induce different components of the local and systemic immune response. This review focuses on the immune basis of current (inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV)) as well as novel vaccine platforms against influenza virus. Particular emphasis will be placed on how each platform induces cross-protection against heterologous influenza viruses, as well as how this immunity compares to and contrasts from the “gold standard” of immunity generated by natural influenza virus infection.

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Long-Acting Neuraminidase Inhibitor Laninamivir Octanoate (CS-8958) versus Oseltamivir as Treatment for Children with Influenza Virus Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01755-09 ◽

2010 ◽

Vol 54 (6) ◽

pp. 2575-2582 ◽

Cited By ~ 112

Author(s):

Norio Sugaya ◽

Yasuo Ohashi

Keyword(s):

Virus Infection ◽

Influenza A ◽

H1n1 Virus ◽

Controlled Trial ◽

Influenza Virus Infection ◽

Neuraminidase Inhibitor ◽

Double Blind ◽

Influenza A H1n1 ◽

B Virus ◽

Long Acting

ABSTRACT We conducted a double-blind, randomized controlled trial to compare a long-acting neuraminidase inhibitor, laninamivir octanoate, with oseltamivir. Eligible patients were children 9 years of age and under who had febrile influenza symptoms of no more than 36-h duration. Patients were randomized to 1 of 3 treatment groups: a group given 40 mg laninamivir (40-mg group), a group given 20 mg laninamivir (20-mg group), and an oseltamivir group. Laninamivir octanoate was administered as a single inhalation. Oseltamivir (2 mg/kg of body weight) was administered orally twice daily for 5 days. The primary end point was the time to alleviation of influenza illness. The primary analysis included 184 patients (61, 61, and 62 in the 40-mg group, 20-mg group, and oseltamivir group, respectively). Laninamivir octanoate markedly reduced the median time to illness alleviation in comparison with oseltamivir in patients infected with oseltamivir-resistant influenza A (H1N1) virus, and the reductions were 60.9 h for the 40-mg group and 66.2 h for the 20-mg group. On the other hand, there were no significant differences in the times to alleviation of illness between the laninamivir groups and oseltamivir group for patients with influenza A (H3N2) or B virus infection. Laninamivir octanoate was well tolerated. The most common adverse events were gastrointestinal events. Laninamivir octanoate was an effective and well-tolerated treatment for children with oseltamivir-resistant influenza A (H1N1) virus infection. Further study will be needed to confirm clinical efficacy against influenza A (H3N2) or B virus infection. Its ease of administration is noteworthy, because a single inhalation is required during the course of illness.

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Quantifying homologous and heterologous antibody titre rises after influenza virus infection

Epidemiology and Infection ◽

10.1017/s0950268816000583 ◽

2016 ◽

Vol 144 (11) ◽

pp. 2306-2316 ◽

Cited By ~ 10

Author(s):

G. FREEMAN ◽

R. A. P. M. PERERA ◽

E. NGAN ◽

V. J. FANG ◽

S. CAUCHEMEZ ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A Virus ◽

Antibody Titre ◽

Influenza A ◽

Haemagglutination Inhibition ◽

Influenza Virus Infection ◽

Virus Infections ◽

Influenza A H1n1 ◽

Antibody Titres

SUMMARYMost influenza virus infections are associated with mild disease. One approach to estimate the occurrence of influenza virus infections in individuals is via repeated measurement of humoral antibody titres. We used baseline and convalescent antibody titres measured by haemagglutination inhibition (HI) and viral neutralization (VN) assays against influenza A(H1N1), A(H3N2) and B viruses to investigate the characteristics of antibody rises following virologically confirmed influenza virus infections in participants in a community-based study. Multivariate models were fitted in a Bayesian framework to characterize the distribution of changes in antibody titres following influenza A virus infections. In 122 participants with PCR-confirmed influenza A virus infection, homologous antibody titres rose by geometric means of 1·2- to 10·2-fold after infection with A(H1N1), A(H3N2) and A(H1N1)pdm09. Significant cross-reactions were observed between A(H1N1)pdm09 and seasonal A(H1N1). Antibody titre rises for some subtypes and assays varied by age, receipt of oseltamivir treatment, and recent receipt of influenza vaccination. In conclusion, we provided a quantitative description of the mean and variation in rises in influenza virus antibody titres following influenza virus infection. The multivariate patterns in boosting of antibody titres following influenza virus infection could be taken into account to improve estimates of cumulative incidence of infection in seroepidemiological studies.

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Impact of influenza virus during pregnancy: from disease severity to vaccine efficacy

Future Virology ◽

10.2217/fvl-2020-0024 ◽

2020 ◽

Vol 15 (7) ◽

pp. 441-453

Author(s):

Ana Vazquez-Pagan ◽

Rebekah Honce ◽

Stacey Schultz-Cherry

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Immune Responses ◽

Pregnant Women ◽

Disease Severity ◽

Influenza A ◽

Antiviral Treatment ◽

Influenza Virus Infection ◽

Severe Influenza ◽

The Impact

Pregnant women are among the individuals at the highest risk for severe influenza virus infection. Infection of the mother during pregnancy increases the probability of adverse fetal outcomes such as small for gestational age, preterm birth and fetal death. Animal models of syngeneic and allogeneic mating can recapitulate the increased disease severity observed in pregnant women and are used to define the mechanism(s) of that increased severity. This review focuses on influenza A virus pathogenesis, the unique immunological landscape during pregnancy, the impact of maternal influenza virus infection on the fetus and the immune responses at the maternal–fetal interface. Finally, we summarize the importance of immunization and antiviral treatment in this population and highlight issues that warrant further investigation.

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A Fungal Cu/Zn-Containing Superoxide Dismutase Enhances the Therapeutic Efficacy of a Plant Polyphenol Extract in Experimental Influenza Virus Infection

Zeitschrift für Naturforschung C ◽

10.1515/znc-2010-5-616 ◽

2010 ◽

Vol 65 (5-6) ◽

pp. 419-428 ◽

Cited By ~ 1

Author(s):

Julia Serkedjieva ◽

Tsvetanka Stefanova ◽

Ekaterina Krumova

Keyword(s):

Superoxide Dismutase ◽

Influenza Virus ◽

Virus Infection ◽

Protective Effect ◽

Influenza A ◽

Influenza Virus Infection ◽

Protective Role ◽

Combined Application ◽

Combined Use ◽

Experimental Influenza

The combined protective effect of a polyphenol-rich extract, isolated from Geranium sanguineum L. (PC), and a novel naturally glycosylated Cu/Zn-containing superoxide dismutase, produced from the fungal strain Humicula lutea 103 (HL-SOD), in the experimental influenza A virus infection (EIVI) in mice, induced with the virus A/Aichi/2/68 (H3N2), was investigated. The combined application of HL-SOD and PC in doses, which by themselves do not defend significantly mice in EIVI, resulted in a synergistically increased protection, determined on the basis of protective indices and amelioration of lung injury. Lung weights and consolidation as well as infectious lung virus titers were all decreased significantly parallel to the reduction of the mortality rates; lung indices were raised. The excessive production of reactive oxygen species (ROS) by alveolar macrophages (aMØ) as well as the elevated levels of the lung antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), induced by EIVI, were brought to normal. For comparative reasons the combined protective effect of PC and vitamin C was investigated. The obtained results support the combined use of antioxidants for the treatment of influenza virus infection and in general indicate the beneficial protective role of combinations of viral inhibitors of natural origin with diverse modes of action.

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Severe Influenza Virus Infection in Children Admitted to the PICU: Comparison of Influenza A and Influenza B Virus Infection

Journal of Medical Virology ◽

10.1002/jmv.27400 ◽

2021 ◽

Author(s):

Pınar YAZICI ÖZKAYA ◽

Eşe Eda TURANLI ◽

Hamdi METİN ◽

Ayça Aydın UYSAL ◽

Candan ÇİÇEK ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Influenza Virus Infection ◽

Influenza B Virus ◽

Influenza B ◽

Severe Influenza ◽

B Virus

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IFITM3 protects the heart during influenza virus infection

10.1101/518548 ◽

2019 ◽

Author(s):

Adam D. Kenney ◽

Temet M. McMichael ◽

Alexander Imas ◽

Nicholas M. Chesarino ◽

Lizhi Zhang ◽

...

Keyword(s):

Heart Rate ◽

Influenza Virus ◽

Virus Infection ◽

Cardiac Dysfunction ◽

Influenza A ◽

Transmembrane Protein ◽

Influenza Virus Infection ◽

Small Animal ◽

Heart Tissue ◽

Underlying Mechanisms

AbstractInfluenza virus primarily targets the lungs, but dissemination and damage to heart tissue is also known to occur in severe infections. Despite this knowledge, influenza virus-induced cardiac pathogenesis and its underlying mechanisms have been difficult to study due to a lack of small animal models. In humans, polymorphisms in the gene encoding interferon-induced transmembrane protein 3 (IFITM3), an antiviral restriction factor, are associated with susceptibility to severe influenza, but whether IFITM3 deficiencies contribute to other aspects of pathogenesis, including cardiac dysfunction, is unknown. We now show that IFITM3 deficiency in a newly generated knockout (KO) mouse model exacerbates illness and mortality following influenza A virus infection. Enhanced pathogenesis correlated with increased replication of virus in the lungs, spleens, and hearts of KO mice relative to wildtype (WT) mice. IFITM3 KO mice exhibited normal cardiac function at baseline, but developed severely aberrant electrical activity upon infection, including decreased heart rate and irregular, arrhythmic RR (interbeat) intervals. In contrast, WT mice exhibited a mild decrease in heart rate without irregularity of RR intervals. Heightened cardiac virus titers and electrical dysfunction in KO animals was accompanied by increased activation of fibrotic pathways and fibrotic lesions in the heart. Our findings reveal an essential role for IFITM3 in controlling influenza virus replication and pathogenesis in heart tissue and establish IFITM3 KO mice as a powerful model to study virus-induced cardiac dysfunction.

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Routine blood parameters are helpful for early identification of influenza infection in children

10.21203/rs.3.rs-54705/v2 ◽

2020 ◽

Author(s):

Ronghe Zhu ◽

Cuie Chen ◽

Qiu Wang ◽

Xixi Zhang ◽

Chaosheng Lu ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A Virus ◽

Early Identification ◽

Influenza A ◽

Influenza Infection ◽

Influenza Virus Infection ◽

Cutoff Value ◽

Routine Blood ◽

Influenza A Virus Infection

Abstract Purpose Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), LYM*PLT and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children.Methods We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 hours of the onset of fever for influenza virus infection.Results The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the >6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the >6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924.Conclusions Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly influenza A virus infection.

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Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

mBio ◽

10.1128/mbio.00246-18 ◽

2018 ◽

Vol 9 (2) ◽

Cited By ~ 16

Author(s):

Mira C. Patel ◽

Kari Ann Shirey ◽

Marina S. Boukhvalova ◽

Stefanie N. Vogel ◽

Jorge C. G. Blanco

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Influenza Virus Infection ◽

High Mobility ◽

Influenza B Virus ◽

Influenza B ◽

Lung Pathology ◽

B Virus ◽

Cotton Rats

ABSTRACT Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI. IMPORTANCE Influenza virus is a common infectious agent causing serious seasonal epidemics, and there is urgent need to develop an alternative treatment modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI.

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