Use of #baloxavir as adjunctive #antiviral #therapy to neuraminidase inhibitors in severely immunocompromised individuals infected with #influenza

 

ABSTRACT

Immunocompromised patients are at risk of developing severe influenza, with protracted viral shedding and development of resistance-associated mutations under antiviral treatment. We report a case series of severely immunocompromised hematology patients, including allogeneic hematopoietic cell transplantation (HCT) recipients, treated with both baloxavir and oseltamivir and describe clinical and virological outcomes and the safety profile of prolonged combination therapy. Allogeneic HCT recipients with influenza infection treated with baloxavir were retrieved via institutional databases. All hospitalized allogeneic HCT patients treated with a combination therapy of baloxavir and oseltamivir over five influenza seasons between October 2019 and May 2025 were included. Six influenza-infected hematology patients (5/6 allogeneic HCT recipients) were treated with combination therapy of oseltamivir and baloxavir. All patients presented with lower respiratory tract infections. Oseltamivir treatment duration ranged from 5 to 31 days, and the number of administered baloxavir doses ranged between one and five. Baloxavir administration was well tolerated, and no adverse events could be attributed to the administered antiviral treatment. All-cause mortality at 3 months post-infection was 66% (4/6), mainly driven by underlying disease. In two patients with protracted shedding, combination therapy did not prevent the development of resistance mutation(s). Combination treatment with prolonged courses of oseltamivir and repeated doses of baloxavir was well tolerated. No definitive conclusions on the efficacy of this approach could be drawn from this study. More data are required on the best treatment of hematology patients infected with influenza.

Source: 

Link: https://journals.asm.org/doi/10.1128/aac.01659-25

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#Report of the 49th meeting of #WHO Global Advisory #Committee on #Vaccine #Safety 27–28 November 2025 (Excerpt, Mar. 6 '26)

 

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COVID-19 current vaccine safety status and insights 

-- Since 2021, GACVS has regularly reviewed the safety of COVID-19 vaccines, including through global pharmacovigilance data and dedicated reviews of myocarditis, pregnancy outcomes and other adverse events of special interest (AESI). 

-- The most recent updates reaffirmed that the benefits of vaccination outweigh the risks across all groups and advised continued monitoring for younger males and follow-up of persons who have reported vaccine-associated myocarditis. 

-- Many individuals have received three or more doses of COVID-19 vaccine. 

-- Some adverse events – such as myocarditis – seem to occur mainly after the second dose of mRNA COVID- 19 vaccines. 

-- However, the outcomes were less severe in persons who developed myocarditis after vaccination compared to those unvaccinated and following infections, including SARS- CoV-2. 

-- Also, children under six months of age seem to be at higher risk of severe COVID-19 infection along with people over the age of 65 years. 

-- WHO has recommended continued vaccination for high-priority groups while acknowledging that gaps remain in the evidence on the safety of repeated dosing, long-term outcomes, and in subgroups such as children and pregnant women. 

-- As of October 2025, for all COVID-19 vaccines, there were only 32 cases of perturbation of fetal development in EudraVigilance, of which most were reported with the original vaccine strains. 

-- An analysis of safety of protein-based COVID-19 vaccines by the Uppsala Monitoring Centre (UMC) showed that as of November 2025 there were almost 6 million reports for all COVID-19 vaccines in UMC’s VigiBase. 

-- Of these, 16 548 reports concerned updated COVID-19 vaccine variants; among these were 5085 reports for updated protein-subunit vaccines. 

-- Around 17.4% of these were serious, and 50 reported a fatal outcome. 

-- Most reports were for the variant NVX CoV 2373 and most deaths were older vaccinees aged 75 years or more. 

-- GACVS reviewed findings from the Scandinavian collaboration called SCOPE (Scandinavian studies of COvid-19 in PrEgnancy). 

-- Findings showed no increased risk of adverse pregnancy, maternal or neonatal outcomes after mRNA COVID-19 vaccination in pregnancy in Denmark, Norway and Sweden. 

-- As of September 2025, the recommendation for vaccination in pregnancy was revised to apply only to specific high-risk groups. 

-- A case-control study by SCOPE of all women with a miscarriage before 14 weeks and all women with a primary care-based confirmation of an ongoing pregnancy in the first trimester revealed no evidence of increased risk of early pregnancy loss after COVID-19 vaccination. 

-- A further investigation of COVID-19 infection and vaccination with mRNA vaccines during the first trimester of pregnancy and the risk of congenital anomalies, in a population-based cohort of 150 000 live-born infants in Denmark, Norway and Sweden, showed no increased risk of major congenital anomalies among infants whose mothers were vaccinated against COVID-19 during the first trimester. 

-- A SCOPE investigation of the association between COVID-19 vaccination and several pregnancy outcomes among a cohort of almost 160 000 singleton pregnancies between January 2021 and 2022 in Norway and Sweden showed that vaccination against COVID-19 during pregnancy was not associated with any of the studied adverse pregnancy outcomes. 

-- In another SCOPE study of COVID-19 vaccination during pregnancy and the risk of severe postpartum haemorrhage, including more than 300 000 single-term deliveries in Denmark, Norway and Sweden, no evidence was found of an association between COVID-19 vaccination at any time during pregnancy and severe postpartum hemorrhage. 

-- Finally, SCOPE investigated neonatal outcomes after COVID-19 vaccination with mRNA vaccine during pregnancy in a cohort of almost 200 000 infants in Norway and Sweden. 

-- Again, no increased odds were found of any adverse neonatal outcomes and neonatal mortality. 

-- In consideration of the evidence presented, GACVS members agreed the following: 

- Repeated-dose safety (including boosters with variant-containing vaccines): 

* Current evidence remains reassuring, with no new safety signals recently identified. 

- Safety of protein-based vaccines: 

* While generally well tolerated, reported adverse events include a proportion of serious individual case safety reports (ICSRs) in the global database. Several potential signals (e.g. tinnitus, antibody-dependent enhancement, thrombosis) require further evaluation. Additional data collection and analysis are therefore recommended to strengthen the evidence base for these vaccines. 

- Long-term outcomes of known risks (e.g. myocarditis, pregnancy outcomes): 

* Myocarditis continues to occur predominantly in younger adults, typically with mild-to- moderate severity and most frequently after the second dose. Longer follow-up studies are needed to define the long-term prognosis and risks of revaccination in affected individuals. 

- Subgroup-specific safety (children, young males, older adults, immunocompromised individuals, pregnant women): 

* Evidence to date shows no harmful effects of mRNA COVID-19 vaccination during pregnancy, including no increase in congenital anomalies, adverse perinatal outcomes, or some post-natal complications. Some studies even suggest lower odds of intracranial haemorrhage, cerebral ischaemia and neonatal mortality among infants of vaccinated mothers. 

- Safety monitoring during the transition to endemic COVID-19 vaccination: 

* Continued vigilance is required, particularly regarding more recent variant-adapted vaccines which remain safe on the basis of current data. Enhanced monitoring of protein-based vaccines is important given the comparatively limited evidence and the presence of identified risks that warrant further investigation.

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Source: 

Link: https://www.who.int/publications/journals/weekly-epidemiological-record

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Updated #Evidence for #Covid19, #RSV, and #Influenza #Vaccines for 2025–2026

 

Abstract

Background

Changes in the vaccine advisory process in the United States have disrupted immunization guidance, which reinforces the need for independent evidence review to inform decisions regarding immunization for respiratory viruses during the 2025–2026 season.

Methods

We conducted a systematic review of U.S.-licensed immunizations against coronavirus disease 2019 (Covid-19), respiratory syncytial virus (RSV), and influenza. We searched databases on PubMed/MEDLINE, Embase, and Web of Science for updates of the most recent review by the Advisory Committee on Immunization Practices (ACIP) Evidence-to-Recommendations for each disease, which was performed during the 2023–2024 period. Outcomes included vaccine efficacy and effectiveness against hospitalization, other clinical end points, and safety.

Results

Of 17,263 identified references, 511 studies met the inclusion criteria. Covid-19 mRNA vaccines against the XBB.1.5 subvariant had pooled vaccine effectiveness against hospitalization of 46% (95% confidence interval [CI], 34 to 55; from cohort studies) and 50% (95% CI, 43 to 57; from case–control studies) among adults and 37% (95% CI, 29 to 44) among immunocompromised adults. In a case–control study, vaccines against the KP.2 subvariant showed an effectiveness of 68% (95% CI, 42 to 82). Maternal RSV vaccination (for infant protection), nirsevimab for infants, and RSV vaccines in adults who were 60 years of age or older showed vaccine effectiveness of 68% or more against hospitalization. Influenza vaccination had a pooled vaccine effectiveness of 48% (95% CI, 39 to 55) in adults between the ages of 18 and 64 years and 67% (95% CI, 58 to 75) in children against hospitalization. Safety profiles were consistent with previous evaluations. The diagnosis of myocarditis associated with Covid-19 vaccines occurred at rates of 1.3 to 3.1 per 100,000 doses in male adolescents, with lower risk associated with longer dosing intervals. The RSVpreF vaccine was associated with 18.2 excess cases of Guillain–Barré syndrome per million doses in older adults; a significant association with preterm birth was not observed when the vaccine was administered at 32 to 36 weeks’ gestation.

Conclusions

Ongoing peer-reviewed evidence supports the safety and effectiveness of immunizations against Covid-19, RSV, and influenza during the 2025–2026 season. (Funded by the Center for Infectious Disease Research and Policy and the Alumbra Innovations Foundation.)

Source: The New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMsa2514268?query=TOC

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#WHO #statement on #autism-related issues (September 23 '25)

 

The World Health Organization (WHO) emphasizes that there is currently no conclusive scientific evidence confirming a possible link between autism and use of acetaminophen (also known as paracetamol) during pregnancy. 

Globally, nearly 62 million people (1 in 127) have autism spectrum disorder, a diverse group of conditions related to development of the brain. Although awareness and diagnosis have improved in recent years, the exact causes of autism have not been established, and it is understood there are multiple factors that can be involved.  

Extensive research has been undertaken over the past decade, including large-scale studies, looking into links between acetaminophen use during pregnancy and autism. At this time, no consistent association has been established. 

WHO recommends that all women continue to follow advice of their doctors or health workers, who can help assess individual circumstances and recommend necessary medicines. Any medicine should be used with caution during pregnancy, especially in the first three months, and in line with advice from health professionals. 

Also, a robust, extensive evidence base exists showing childhood vaccines do not cause autism. Large, high-quality  studies from many countries have all reached the same conclusion. Original studies suggesting a link were flawed and have been discredited. Since 1999, independent experts advising WHO have repeatedly confirmed that vaccines—including those with thiomersal or aluminum—do not cause autism or other developmental disorders.   

Childhood vaccine schedules are developed through a careful, extensive and evidence-based process involving global experts and country input. The childhood immunization schedule, carefully guided by WHO, has been adopted by all countries, and has saved at least 154 million lives over the past 50 years. The schedule remains essential for the health and wellbeing of every child and every community. These schedules have continually evolved with science and now safeguard children, adolescents and adults against 30 infectious diseases.  

Every vaccine recommendation by the Strategic Advisory Group of Experts on Immunization (SAGE), an independent advisory group to WHO, is grounded in rigorous review of evidence and carefully designed to offer the best protection against serious diseases and to be delivered when most needed.   

When immunization schedules are delayed or disrupted, or altered without evidence review, there is a sharp increase in the risk of infection not only for the child, but also for the wider community. Infants too young to be vaccinated and people with weakened immune systems or underlying health conditions are at greatest risk.  

Autism and neurodevelopmental disorders are among priority mental health and neurological conditions being discussed at the 4th UN High-Level Meeting on NCDs and mental health this Thursday, 25 September.  As a global community, we need to do more to understand the causes of autism and how best to care for and support the needs of autistic people and their families.   

WHO is committed to advancing this goal working together with partners including autistic-led organizations and other organizations representing persons with lived experience. WHO also stands with people who are living with autism and their families, a dignified community entitled to evidence-based considerations free of stigma.

Source: World Health Organization, https://www.who.int/news/item/24-09-2025-who-statement-on-autism-related-issues

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#Placental transfer of #medications to treat #COVID19, #molnupiravir, #favipiravir and #nirmatrelvir/ritonavir, in the ex vivo human cotyledon model

 

Abstract

Objectives

There have been few studies in pregnant women of medications that are used to reduce severe complications from COVID-19 infection. Currently, nirmatrelvir/ritonavir (Paxlovid) is recommended by the National Institutes for Health to treat non-hospitalized pregnant patients with mild-to-moderate COVID-19 illness. The aim of this study was to determine the transplacental passage of molnupiravir, nirmatrelvir/ritonavir and favipiravir utilizing an ex vivo placental perfusion model.

Methods

Human placental cotyledons were continuously perfused in a double open circuit. The study molecules and antipyrine, a marker of placental viability, were dissolved in the maternal solution. The experiment was conducted over 90 minutes, and every 5 minutes, samples of the maternal solution and fetal exchange solutions were collected for analysis. We calculated the concentrations of study molecules, fetal transfer ratios and the clearance indexes to determine placental transfer.

Results

Of 18 placentas analysed, 14 were validated by antipyrine transfer. Nirmatrelvir alone had low placental transfer, with a fetal transfer ratio of 0.025. Its placenta transfer increased in the presence of ritonavir, with a fetal transfer ratio of 0.06. The molnupiravir metabolite, β-D-N-4-hydroxycytidine (EIDD 1931), showed low placental transfer, with an average fetal transfer ratio of 0.04. By contrast, favipiravir crossed the placenta with an average fetal transfer ratio of 0.425.

Conclusions

Placental transfer was high for the nucleoside analogue favipiravir, while it was low for molnupiravir and low for the protease inhibitor nirmatrelvir but increased by ritonavir. Clinical data are required to confirm the placental transfer and determine the safety of COVID antivirals in pregnancy.

Source: Journal of Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article-abstract/doi/10.1093/jac/dkaf302/8245204?redirectedFrom=fulltext

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