Skip to main content

Host #Immunomodulatory Interventions in Severe #Influenza

Image
By G.M.

 


Abstract

Currently, no immunomodulatory agents have been conclusively shown to benefit severe influenza. The World Health Organization conditionally advises against the use of systemic corticosteroids, macrolides, plasma therapy, mechanistic target of rapamycin inhibitors, and nonsteroidal anti-inflammatory drugs for such patients. High-dose systemic corticosteroids may increase mortality and morbidity in severe influenza; the potential of low-dose corticosteroids merits further study given survival benefits in patients with severe coronavirus disease 2019 (COVID-19). Passive immunotherapy using convalescent plasma or intravenous immunoglobulin (IVIG) from healthy donors has not proven effective, suggesting that future research should focus on hyperimmune plasma or IVIG from recent infections. An open-label randomized controlled trial (RCT) found that a triple combination of oseltamivir, clarithromycin, and naproxen improved outcomes in severe influenza. One RCT has indicated that sirolimus with corticosteroids can expedite liberation from mechanical ventilation and reduce viral load, warranting larger trials of sirolimus alone. In contrast, adding macrolides or nitazoxanide has not consistently improved clinical outcomes. Promising evidence exists for anti-C5a antibodies in COVID-19, while case reports hint that intravenous N-acetylcysteine may benefit severe influenza pneumonia. Observational data on statins remain conflicting. Further studies on COX-2 inhibitors in combination with antivirals and other immunomodulators are needed. Mycophenolic acid, pamidronate, and peroxisome proliferator-activated receptor gamma agonists are low priorities due to toxicity concerns. Research into human mesenchymal stromal cells and herbal medicine remains inconclusive. Overall, these findings support large-scale trials to validate promising results and address limitations in small studies. Treatment of severe influenza requires a multidisciplinary approach that integrates antiviral and immunomodulatory strategies. Clarifying these roles may enhance patient outcomes.

Source: Journal of Infectious Diseases, https://academic.oup.com/jid/article/232/Supplement_3/S262/8287912

____

Labels:

Comments

Post a Comment

Popular posts from this blog

#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

By G.M.
{Excerpt} A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments : M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic , expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries . The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat .1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts , including vertical transmissions , neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential .5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in ext...
Post a Comment
Read more »

No evidence of immune #exhaustion after repeated #SARS-CoV-2 #vaccination in vulnerable and healthy populations

By G.M.
Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion , which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada . Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was...
Post a Comment
Read more »

Chimeric #hemagglutinin and #M2 #mRNA #vaccine for broad #influenza subtype protection

By G.M.
Abstract Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics , developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy , we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs , as well as highly pathogenic avian influenza . Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies , T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries . In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells . Moreover, Fluaxe immuniza...
Post a Comment
Read more »