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Viruses Nov 2023Influenza can cause respiratory infections, leading to significant morbidity and mortality in humans. While current influenza vaccines offer varying levels of...
Influenza can cause respiratory infections, leading to significant morbidity and mortality in humans. While current influenza vaccines offer varying levels of protection, there remains a pressing need for effective antiviral drugs to supplement vaccine efforts. Currently, the FDA-approved antiviral drugs for influenza include oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These antivirals primarily target the virus, making them vulnerable to drug resistance. In this study, we evaluated the efficacy of the neuraminidase inhibitor, oseltamivir, against probenecid, which targets the host cells and is less likely to engender resistance. Our results show that probenecid has superior antiviral efficacy compared to oseltamivir in both in vitro replication assays and in vivo mouse models of influenza infection.
Topics: Humans; Animals; Mice; Oseltamivir; Influenza, Human; Probenecid; Influenza Vaccines; Antiviral Agents; Enzyme Inhibitors; Virus Replication; Neuraminidase; Drug Resistance, Viral
PubMed: 38140606
DOI: 10.3390/v15122366 -
Frontiers in Immunology 2023Influenza A, the most common subtype, induces 3 to 5 million severe infections and 250,000 to 500,000 deaths each year. Vaccination is traditionally considered to be the... (Review)
Review
Influenza A, the most common subtype, induces 3 to 5 million severe infections and 250,000 to 500,000 deaths each year. Vaccination is traditionally considered to be the best way to prevent influenza A. Yet because the Influenza A virus (IAV) is highly susceptible to antigenic drift and Antigenic shift, and because of the lag in vaccine production, this poses a significant challenge to vaccine effectiveness. Additionally, much information about the resistance of antiviral drugs, such as Oseltamivir and Baloxavir, has been reported. Therefore, the search for alternative therapies in the treatment of influenza is warranted. Recent studies have found that regulating the gut microbiota (GM) can promote the immune effects of anti-IAV via the gut-lung axis. This includes promoting IAV clearance in the early stages of infection and reducing inflammatory damage in the later stages. In this review, we first review the specific alterations in GM observed in human as well as animal models regarding IAV infection. Then we analyzed the effect of GM on host immunity against IAV, including innate immunity and subsequent adaptive immunity. Finally, our study also summarizes the effects of therapies using probiotics, prebiotics, or herbal medicine in influenza A on intestinal microecological composition and their immunomodulatory effects against IAV.
Topics: Animals; Humans; Influenza, Human; Orthomyxoviridae Infections; Gastrointestinal Microbiome; Lung; Influenza A virus
PubMed: 37928517
DOI: 10.3389/fimmu.2023.1147724 -
MMWR. Morbidity and Mortality Weekly... Oct 2023On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to...
Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years - IVY Network, 20 U.S. States, February 2022-May 2023.
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.
Topics: Humans; Aged; COVID-19; Influenza, Human; SARS-CoV-2; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Hospitalization; Patient Acuity; Oxygen
PubMed: 37796753
DOI: 10.15585/mmwr.mm7240a2 -
Antiviral Research Aug 2023Our previous study shows favipiravir and oseltamivir combination therapy may accelerate clinical recovery compared to oseltamivir monotherapy in severe influenza, but...
Our previous study shows favipiravir and oseltamivir combination therapy may accelerate clinical recovery compared to oseltamivir monotherapy in severe influenza, but its effect on virological evolution and resistance mutation against oseltamivir is still unknown. In this study, we collected longitudinal respiratory samples from influenza patients who underwent combination therapy and applied them to next generation sequencing of the whole genome of the influenza A virus (IAV). We also included a cohort untreated with any antivirals to serve as the control. In total, 62 samples from 19 patients treated with combination therapy and 20 samples from 20 patients untreated were successfully sequenced. The nucleotide diversity in the whole genome of IAV in the combination group showed no difference compared to that in the control group (P > 0.05). Moreover, we observed 174 kinds of nonsynonymous nucleotide substitutions in patients with combination therapy, mostly in NA (n = 44) and HA (n = 43). Of them, the G→A transition was the dominant variant type (27%) and 46/174 (26%) was reported to have biological effects, such as increased pathogenicity and polymerase activity. Among the 29 mutations conferring reduction in oseltamivir sensitivity we investigated, H275Y was the only mutation detected in the 4 samples from 1 of 19 patients and demonstrated increasing frequency during the treatment. Mutations conferring favipiravir resistance were not observed. Our studies showed combination therapy of favipiravir and oseltamivir has little effect on virus nucleotide diversity, nor prevents the increase of oseltamivir-resistant variants.
Topics: Humans; Oseltamivir; Influenza, Human; Influenza A virus; Influenza A Virus, H1N1 Subtype; Drug Resistance, Viral; Antiviral Agents; Neuraminidase
PubMed: 37369282
DOI: 10.1016/j.antiviral.2023.105657 -
The Medical Letter on Drugs and... Nov 2023
Topics: Humans; Antiviral Agents; Influenza, Human; Enzyme Inhibitors; Neuraminidase; Oseltamivir; Zanamivir
PubMed: 37935018
DOI: 10.58347/tml.2023.1689a -
Current Opinion in Hematology Nov 2023The platelet surface harbors a lush forest of glycans (carbohydrate polymers) attached to membrane proteins and lipids. Accumulating evidence suggests that these glycans... (Review)
Review
PURPOSE OF REVIEW
The platelet surface harbors a lush forest of glycans (carbohydrate polymers) attached to membrane proteins and lipids. Accumulating evidence suggests that these glycans may be relevant to the pathophysiology of immune thrombocytopenia (ITP). Here, we critically evaluate data that point to a possible role for loss of sialic acid in driving platelet clearance in ITP, comment on the potential use of neuraminidase inhibitors for treatment of ITP, and highlight open questions in this area.
RECENT FINDINGS
Multiple lines of evidence suggest a role for loss of platelet sialic acid in the pathophysiology of thrombocytopenia. Recent work has tested the hypothesis that neuraminidase-mediated cleavage of platelet sialic acid may trigger clearance of platelets in ITP. Some clinical evidence supports efficacy of the viral neuraminidase inhibitor oseltamivir in ITP, which is surprising given its lack of activity against human neuraminidases.
SUMMARY
Further study of platelet glycobiology in ITP is necessary to fill key knowledge gaps. A deeper understanding of the roles of platelet glycans in ITP pathophysiology will help to guide development of novel therapies.
Topics: Humans; Antiviral Agents; Blood Platelets; Glycomics; N-Acetylneuraminic Acid; Neuraminidase; Polysaccharides; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
PubMed: 37526945
DOI: 10.1097/MOH.0000000000000781 -
The Medical Letter on Drugs and... Nov 2023
Topics: Humans; Antiviral Agents; Influenza, Human; Enzyme Inhibitors; Neuraminidase; Oseltamivir; Zanamivir
PubMed: 37935021
DOI: 10.58347/tml.2023.1689e -
Clinical and Experimental Medicine Nov 2023COVID-19 has impacted populations across the globe and has been a major cause of morbidity and mortality. Influenza is another potentially deadly respiratory infection... (Review)
Review
COVID-19 has impacted populations across the globe and has been a major cause of morbidity and mortality. Influenza is another potentially deadly respiratory infection that affects people worldwide. While both of these infections pose major health threats, little is currently understood regarding the clinical aspects of influenza and COVID-19 co-infection. Our objective was to therefore provide a systematic review of the clinical characteristics, treatments, and outcomes for patients who are co-infected with influenza and COVID-19. Our review, which was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, involved searching for literature in seven different databases. Studies were eligible for inclusion if they included at least one co-infected patient, were available in English, and described clinical characteristics for the patients. Data were pooled after extraction. Study quality was assessed using the Joanna Brigg's Institute Checklists. Searches produced a total of 5096 studies, and of those, 64 were eligible for inclusion. A total of 6086 co-infected patients were included, 54.1% of whom were male; the mean age of patients was 55.9 years (SD = 12.3). 73.6% of cases were of influenza A and 25.1% were influenza B. 15.7% of co-infected patients had a poor outcome (death/deterioration). The most common symptoms were fever, cough, and dyspnea, with the most frequent complications being pneumonia, linear atelectasis, and acute respiratory distress syndrome. Oseltamivir, supplemental oxygen, arbidol, and vasopressors were the most common treatments provided to patients. Having comorbidities, and being unvaccinated for influenza, were shown to be important risk factors. Co-infected patients show symptoms that are similar to those who are infected with COVID-19 or influenza only. However, co-infected patients have been shown to be at an elevated risk for poor outcomes compared to mono-infected COVID-19 patients. Screening for influenza in high-risk COVID-19 patients is recommended. There is also a clear need to improve patient outcomes with more effective treatment regimens, better testing, and higher rates of vaccination.
Topics: Humans; Male; Middle Aged; Female; COVID-19; Influenza, Human; SARS-CoV-2; Coinfection; Comorbidity
PubMed: 37326928
DOI: 10.1007/s10238-023-01116-y -
Med (New York, N.Y.) Jan 2024Recent outbreaks of avian influenza and ongoing virus reassortment have drawn focus on spill-over infections. The increase in human infections with highly pathogenic...
BACKGROUND
Recent outbreaks of avian influenza and ongoing virus reassortment have drawn focus on spill-over infections. The increase in human infections with highly pathogenic avian influenza H5N6 virus and its high fatality rate posed a potential threat, necessitating the search for a more effective treatment.
METHODS
Longitudinal clinical data and specimens were collected from five H5N6 patients after admission. All patients received antiviral treatment of either sequential monotherapy of oseltamivir and baloxavir or the two drugs in combination. Severity of illness; viral load in sputum, urine, and blood; and cytokine levels in serum and sputum were serially analyzed.
FINDINGS
All patients developed acute respiratory distress syndrome (ARDS) and viral sepsis within 1 week after disease onset. When delayed oseltamivir showed poor effects, baloxavir was administered and rapidly decreased viral load. In addition, levels of IL-18, M-CSF, IL-6, and HGF in sputum and Mig and IL-18 in serum that reflected ARDS and sepsis deterioration, respectively, were also reduced with baloxavir usage. However, three patients eventually died from exacerbation of underlying disease and secondary bacterial infection. Nonsurvivors had more severe extrapulmonary organ dysfunction and insufficient H5N6 virus-specific antibody response.
CONCLUSIONS
For critical human cases of H5N6 infection, baloxavir demonstrated effects on viral load and pulmonary/extrapulmonary cytokines, even though treatment was delayed. Baloxavir could be regarded as a first-line treatment to limit continued viral propagation, with potential future application in avian influenza human infections and poultry workers exhibiting influenza-like illness.
FUNDING
This work was funded by the National Natural Science Foundation of China (81761128014).
Topics: Animals; Humans; Influenza in Birds; Oseltamivir; Influenza A Virus, H5N6 Subtype; Interleukin-18; Influenza, Human; Influenza A virus; Respiratory Distress Syndrome; Sepsis; Dibenzothiepins; Morpholines; Pyridones; Triazines
PubMed: 38070511
DOI: 10.1016/j.medj.2023.11.001 -
Revue Medicale Suisse Jan 2024The year 2023 saw the publication of several studies in various areas of infectious diseases. The administration of corticosteroids decreased mortality in severe... (Meta-Analysis)
Meta-Analysis
The year 2023 saw the publication of several studies in various areas of infectious diseases. The administration of corticosteroids decreased mortality in severe community-acquired pneumonia. Administration of doxycycline post-exposure prophylaxis reduced the risk of bacterial sexually transmitted infections at the risk of resistance selection. An herbal preparation decreased mortality in sepsis. A meta-analysis concludes that oseltamivir does not significantly reduce the risk of hospitalisation for influenza. Discontinuation of antibiotic prophylaxis during dental procedures in Sweden did not increase the incidence of viridans group Streptococcus endocarditis. Several studies have led to the introduction of RSV (Respiratory Syncytial Virus (RSV) vaccination. 2023 also saw the resurgence of invasive Group A Streptococcal infections, of which clinicians must be wary.
Topics: Humans; Communicable Diseases; Sepsis; Streptococcal Infections; Influenza, Human; Doxycycline
PubMed: 38231101
DOI: 10.53738/REVMED.2024.20.856-7.55