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Science Advances Feb 2024Seasonal or pandemic illness caused by influenza A viruses (IAVs) is a major public health concern due to the high morbidity and notable mortality. Although there are...
Seasonal or pandemic illness caused by influenza A viruses (IAVs) is a major public health concern due to the high morbidity and notable mortality. Although there are several approved drugs targeting different mechanisms, the emergence of drug resistance calls for new drug candidates that can be used alone or in combinations. Small-molecule IAV entry inhibitor, ING-1466, binds to hemagglutinin (HA) and blocks HA-mediated viral infection. Here, we show that this inhibitor demonstrates preventive and therapeutic effects in a mouse model of IAV with substantial improvement in the survival rate. When administered orally it elicits a therapeutic effect in mice, even after the well-established infection. Moreover, the combination of ING-1466 with oseltamivir phosphate or baloxavir marboxil enhances the therapeutic effect in a synergistic manner. Overall, ING-1466 has excellent oral bioavailability and in vitro absorption, distribution, metabolism, excretion, and toxicity profile, suggesting that it can be developed for monotherapy or combination therapy for the treatment of IAV infections.
Topics: Animals; Mice; Oseltamivir; Influenza A virus; Antiviral Agents; Oxazines; Pyridines; Thiepins; Dibenzothiepins; Morpholines; Pyridones; Triazines
PubMed: 38394202
DOI: 10.1126/sciadv.adk9004 -
Haematologica Jun 2024
Topics: Humans; Oseltamivir; Male; Female; Antiviral Agents; Platelet Count; Hospitalization; Blood Platelets; Databases, Factual; Middle Aged; Aged; Adult; Influenza, Human; COVID-19 Drug Treatment
PubMed: 38385256
DOI: 10.3324/haematol.2023.283731 -
International Journal of Antimicrobial... Apr 2024Oseltamivir is a low-cost antiviral agent that could support or complement treatment of COVID-19. This study assessed whether oseltamivir is effective in reducing...
BACKGROUND
Oseltamivir is a low-cost antiviral agent that could support or complement treatment of COVID-19. This study assessed whether oseltamivir is effective in reducing COVID-19-related mortality.
METHODS
This retrospective cohort study evaluated real-world data from a nationwide database of hospitalisation due to severe acute respiratory syndrome in Brazil. Propensity score matching was used to mimic a randomised controlled trial with 'oseltamivir' and 'no antivirals at all' as the intervention and control groups, respectively.
RESULTS
A total of 21 480 and 268 486 patients admitted between February 2020 and January 2023 were included in the intervention and control groups, respectively. After matching, the odds ratio (OR) for death was 0.901 (95% confidence interval [CI] 0.873-0.930). The OR (95% CI) for death in patients who were admitted to the ICU, and on non-invasive or invasive ventilation was 0.868 (0.821-0.917), 0.935 (0.893-0.980), and 0.883 (0.814-0.958), respectively.
CONCLUSIONS
Overall, the use of oseltamivir was associated with an attributable risk reduction of 2.50% (95% CI 1.77-3.29). Similar results were observed in patients who were admitted to the ICU, and on non-invasive or invasive ventilation. Oseltamivir is a low-cost potential antiviral treatment for COVID-19.
Topics: Humans; Antiviral Agents; COVID-19; Hospital Mortality; Oseltamivir; Retrospective Studies; Randomized Controlled Trials as Topic
PubMed: 38354825
DOI: 10.1016/j.ijantimicag.2024.107111 -
Cureus Jan 2024Background The COVID-19 pandemic has posed an unprecedented challenge to the global healthcare system, necessitating effective therapeutic strategies to mitigate its...
Background The COVID-19 pandemic has posed an unprecedented challenge to the global healthcare system, necessitating effective therapeutic strategies to mitigate its impact. This study investigates the significance of early antiviral therapy in the context of intensive care units (ICUs) and its potential to influence the progression and outcomes of severe COVID-19 cases. Methodology This retrospective cohort study leveraged a diverse patient population with confirmed severe COVID-19 admitted to ICUs. A total of 1,250 patients were included in the analysis, and their medical records were comprehensively reviewed. The study aimed to assess the impact of early antiviral therapy on patient outcomes, focusing on the administration of remdesivir within the first 48 hours of ICU admission. Results In a study of 1,250 COVID-19 patients, early antiviral therapy with remdesivir significantly reduced ICU admissions by 30% (N = 225) compared to standard care (N = 525). The early therapy group also exhibited a 20% lower mortality rate (N = 120) than the control group (N = 150). Demographic associations with antiviral usage were observed. Kaletra was favored by females, non-Saudi individuals, and healthcare workers, while favipiravir was associated with gender. Remdesivir and ribavirin use were linked to gender and Saudi nationality, while oseltamivir was related to gender, Saudi nationality, and body mass index. Microbiological cure rates were 15.4%, with 84.6% not achieving it. ICU outcomes included 37.7% deaths, 55.7% home discharges, and 6.6% transfers, while hospital outcomes featured 38.5% deaths, 54.4% home discharges, and 7.1% transfers. Conclusions This study presents a comprehensive analysis of COVID-19 patient demographics, antiviral medication associations, and clinical outcomes. The findings highlight the significance of tailoring treatment strategies based on patient characteristics and viral history. These insights contribute to a deeper understanding of COVID-19 management and can inform clinical decision-making and further research in this field.
PubMed: 38344559
DOI: 10.7759/cureus.52096 -
Journal of Veterinary Science Jan 2024Canine parvoviral enteritis (CPE) is a fatal disease worldwide. The treatment of CPE is based mainly on supportive and symptomatic treatment. Antiviral addition to the...
BACKGROUND
Canine parvoviral enteritis (CPE) is a fatal disease worldwide. The treatment of CPE is based mainly on supportive and symptomatic treatment. Antiviral addition to the treatment may result in a higher survival.
OBJECTIVES
This study evaluated the effects of antiviral treatments with a standardized treatment (ST) on the clinical and inflammatory response of dogs with naturally occurring CPE.
METHODS
Twenty-eight dogs with CPE caused by canine parvovirus type 2 were divided randomly into treatment groups. The ST group received fluid, antibiotic, antiemetic, and deworming treatments. The antiviral treatment groups received the same ST with an additional antiviral drug, recombinant feline interferon omega (rFeIFN-ω), oseltamivir (OSEL) or famciclovir (FAM).
RESULTS
Compared to the healthy control, the tumor necrosis factor-α, interleukin-1β, interferon (IFN)-α, IFN-γ, haptoglobin, and C-reactive protein values were high ( < 0.05) on day zero. At presentation, mild lymphopenia, neutropenia, and a high neutrophil to lymphocyte (LYM) ratio (NLR) were also observed. Adding rFeIFN-ω to the ST produced the best improvement in the clinical score with a decreased NLR, while leucocytes remained low and inflammatory markers stayed high on day three. The survival rates of the groups were 85.7% in ST+IFN, 71.4% in ST+OSEL, 71.4% in ST+FAM, and 57.1% in ST groups on day seven.
CONCLUSIONS
Antiviral drugs may be valuable in treating CPE to improve the clinical signs and survival. In addition, the decrease in NLR in favor of LYM may be an indicator of the early prognosis before the improvement of leukocytes, cytokines, and acute phase proteins in CPE.
Topics: Animals; Dogs; Cats; Parvoviridae Infections; Parvovirus, Canine; Oseltamivir; Antiviral Agents; Enteritis; Dog Diseases; Cat Diseases
PubMed: 38311324
DOI: 10.4142/jvs.23139 -
Influenza and Other Respiratory Viruses Jan 2024During the 2019 severe influenza season, New South Wales (NSW) experienced the highest number of cases in Australia. This study retrospectively investigated the genetic...
BACKGROUND
During the 2019 severe influenza season, New South Wales (NSW) experienced the highest number of cases in Australia. This study retrospectively investigated the genetic characteristics of influenza viruses circulating in NSW in 2019 and identified genetic markers related to antiviral resistance and potential virulence.
METHODS
The complete genomes of influenza A and B viruses were amplified using reverse transcription-polymerase chain reaction (PCR) and sequenced with an Illumina MiSeq platform.
RESULTS
When comparing the sequencing data with the vaccine strains and reference sequences, the phylogenetic analysis revealed that most NSW A/H3N2 viruses (n = 68; 94%) belonged to 3C.2a1b and a minority (n = 4; 6%) belonged to 3C.3a. These viruses all diverged from the vaccine strain A/Switzerland/8060/2017. All A/H1N1pdm09 viruses (n = 20) showed genetic dissimilarity from vaccine strain A/Michigan/45/2015, with subclades 6B.1A.5 and 6B.1A.2 identified. All B/Victoria-lineage viruses (n = 21) aligned with clade V1A.3, presenting triple amino acid deletions at positions 162-164 in the hemagglutinin protein, significantly diverging from the vaccine strain B/Colorado/06/2017. Multiple amino acid substitutions were also found in the internal proteins of influenza viruses, some of which have been previously reported in hospitalized influenza patients in Thailand. Notably, the oseltamivir-resistant marker H275Y was present in one immunocompromised patient infected with A/H1N1pdm09 and the resistance-related mutation I222V was detected in another A/H3N2-infected patient.
CONCLUSIONS
Considering antigenic drift and the constant evolution of circulating A and B strains, we believe continuous monitoring of influenza viruses in NSW via the high-throughput sequencing approach provides timely and pivotal information for both public health surveillance and clinical treatment.
Topics: Humans; Influenza, Human; Retrospective Studies; Herpesvirus 1, Cercopithecine; Influenza A Virus, H3N2 Subtype; New South Wales; Phylogeny; Hemagglutinin Glycoproteins, Influenza Virus; Influenza Vaccines; Australia; Seasons; Whole Genome Sequencing
PubMed: 38288510
DOI: 10.1111/irv.13252 -
Cureus Dec 2023Pulmonary embolisms (PEs) are potentially life-threatening emergencies that carry significant morbidity and mortality. Advances in treatment options and the safety of...
Pulmonary embolisms (PEs) are potentially life-threatening emergencies that carry significant morbidity and mortality. Advances in treatment options and the safety of existing procedures have effectively reduced the long-term and short-term effects of the condition. Therefore, it is important to make an early diagnosis so that treatment options can be thoroughly explored. The D-dimer is an important tool in the early diagnosis of PEs. It is especially useful in ruling out the diagnosis in patients with a low to moderate suspicion of the disease. We present a case of a 22-year-old male who presented with exertional dyspnea, congestion, and rhinorrhea for one day and was noted to have persistent hypoxia and tachycardia. The influenza test was positive, and he was started on oseltamivir. Due to persistent hypoxia, a CT pulmonary angiogram was ordered and revealed filling defects in the left lower lobe segmental vessels suggestive of PE, as well as multifocal multilobar bilateral ground-glass opacities. He was initially treated with a heparin drip and subsequently switched to eliquis. After a significant improvement in his hypoxia, he was discharged home for outpatient follow-up, including a hypercoagulable workup. This case demonstrates that despite the usefulness of the D-dimer as a diagnostic tool for PEs, it cannot solely or fully replace the full gamut of screening tools used to determine the risk of PE. Although rare, false-negative scores do occur; therefore, the tool should always be used in conjunction with other scoring systems, physician gestalt, and within the specific clinical context.
PubMed: 38264382
DOI: 10.7759/cureus.51045 -
Frontiers in Medicine 2023The occurrence of a co-infection involving four distinct respiratory pathogens could be underestimated. Here, we report the case of a 72-year-old woman who presented to...
The occurrence of a co-infection involving four distinct respiratory pathogens could be underestimated. Here, we report the case of a 72-year-old woman who presented to a community hospital with a cough productive of sputum as her main clinical manifestation. Antibody detection of common respiratory pathogens revealed potential co-infection with influenza A, influenza B, respiratory syncytial virus, and . We treated her with 75 mg oseltamivir phosphate administered orally twice daily for 5 days, 0.5 g azithromycin administered orally for 5 days, and 0.3 g acetylcysteine aerosol inhaled twice daily for 3 days. The patient showed a favorable outcome on the eighth day after early diagnosis and treatment. Since co-infection with these four pathogens is rare, we performed an extensive PubMed search of similar cases and carried out a systematic review to analyze the epidemiology, clinical manifestations, transmission route, susceptible population, and outcomes of these four different pathogens. Our report highlights the importance for general practitioners to be vigilant about the possibility of mixed infections when a patient presents with respiratory symptoms. Although these symptoms may be mild, early diagnosis and timely treatment could improve outcomes. Additionally, further research is warranted to explore the potential influence of SARS-CoV-2 infection on the co-occurrence of multiple respiratory pathogens.
PubMed: 38259842
DOI: 10.3389/fmed.2023.1325482 -
Investigative Ophthalmology & Visual... Jan 2024Whether H1N1 infection-associated ocular manifestations result from direct viral infections or systemic complications remains unclear. This study aimed to...
PURPOSE
Whether H1N1 infection-associated ocular manifestations result from direct viral infections or systemic complications remains unclear. This study aimed to comprehensively elucidate the underlying causes and mechanism.
METHOD
TCID50 assays was performed at 24, 48, and 72 hours to verify the infection of H1N1 in human retinal microvascular endothelial cells (HRMECs). The changes in gene expression profiles of HRMECs at 24, 48, and 72 hours were characterized using RNA sequencing technology. Differentially expressed genes (DEGs) were validated using real-time quantitative polymerase chain reaction and Western blotting. CCK-8 assay and scratch assay were performed to evaluate whether there was a potential improvement of proliferation and migration in H1N1-infected cells after oseltamivir intervention.
RESULTS
H1N1 can infect and replicate within HRMECs, leading to cell rounding and detachment. After H1N1 infection of HRMECs, 2562 DEGs were identified, including 1748 upregulated ones and 814 downregulated ones. These DEGs primarily involved in processes such as inflammation and immune response, cytokine-cytokine receptor interaction, signal transduction regulation, and cell adhesion. The elevated expression levels of CXCL10, CXCL11, CCL5, TLR3, C3, IFNB1, IFNG, STAT1, HLA, and TNFSF10 after H1N1 infection were reduced by oseltamivir intervention, reaching levels comparable to those in the uninfected group. The impaired cell proliferation and migration after H1N1 infection was improved by oseltamivir intervention.
CONCLUSIONS
This study confirmed that H1N1 can infect HRMECs, leading to the upregulation of chemokines, which may cause inflammation and destruction of the blood-retina barrier. Moreover, early oseltamivir administration may reduce retinal inflammation and hemorrhage in patients infected with H1N1.
Topics: Humans; Endothelial Cells; Influenza A Virus, H1N1 Subtype; Influenza, Human; Oseltamivir; Retina; Inflammation
PubMed: 38252524
DOI: 10.1167/iovs.65.1.38