Intravenous #immunoglobulin #treatment for #longCOVID: a case report of clinical and immunological findings

 

Summary

A previously healthy 39-year-old man developed highly symptomatic post-COVID-19 condition (also known as long COVID) marked by cognitive dysfunction, disabling fatigue, and autonomic symptoms unresponsive to multiple multidisciplinary interventions. Given the presence of markedly elevated serum autoantibodies against G protein-coupled receptors, high-dose intravenous immunoglobulin therapy was initiated at 400 mg/kg per day for 5 consecutive days. After 4 weeks, a maintenance dose of 500 mg/kg was administered for 1 day, followed by two further maintenance cycles consisting of 500 mg/kg per day for 3 consecutive days, each given at 4-week intervals. In parallel, the patient underwent a cognitive stimulation intervention. Neurological symptoms were assessed with the Fatigue Assessment Scale and the WHO Disability Assessment Schedule 2.0, and the immunological profile was longitudinally analysed during intravenous immunoglobulin treatment. Fatigue scores normalised, neurocognitive performance returned to normal value, and quality of life improved after the first infusion and fully recovered within 1 year. Immunological profiling revealed the presence of an inverted CD4 to CD8 T-cell ratio that persisted during the whole follow-up. We also identified a CD8+ T cell–monocyte complex and spontaneous IFNγ release. Intravenous immunoglobulin therapy was associated with a significant reduction of these complexes, spontaneous IFNγ and TNF production, markers of endothelial inflammation, and circulating autoantibody titres. This patient provides exploratory evidence that high-dose intravenous immunoglobulin was associated with sustained clinical recovery from long COVID over 1 year of follow-up, accompanied by immunological changes consistent with modulation of post-viral immune dysregulation, including a reduction in pathogenic T cell–monocyte synapses. Although causal inference cannot be established from a single patient, these findings suggest that this cellular interaction can contribute to long COVID and that immunomodulation could represent a rational therapeutic approach to be evaluated in selected patients.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00063-0/abstract?rss=yes

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Trained ILCs confer adaptive #immunity-independent #protection against #influenza

ABSTRACT

Seasonal influenza causes 290,000–650,000 deaths annually, with vaccination efficacy ranging from 10 to 60%. The emergence of drug-resistant and highly pathogenic avian influenza viruses underscores the urgent need for novel protective strategies. Epidemiological observations have long suggested that certain vaccines, such as Bacillus Calmette-Guérin (BCG), can provide protection against diverse pathogens (S. Biering-Sørensen, P. Aaby, N. Lund, et al., Clin Infect Dis 65:1183–1190, 2017, https://doi.org/10.1093/cid/cix525; M.-L. Garly, C. L. Martins, C. Balé, et al., Vaccine 21:2782–2790, 2003, https://doi.org/10.1016/s0264-410x(03)00181-6; C. A. G. Timmermann, S. Biering‐Sørensen, P. Aaby, et al., Trop Med Int Health 20:1733–1744, 2015, https://doi.org/10.1111/tmi.12614). While the cellular and molecular mechanisms underlying such protection remain incompletely understood, emerging research offers critical insights into innate immune system modulation (B. Cirovic, L. C. J. de Bree, L. Groh, et al., Cell Host Microbe 28:322–334, 2020, https://doi.org/10.1016/j.chom.2020.05.014; L. Kong, S. J. C. F. M. Moorlag, A. Lefkovith, et al., Cell Rep 37:110028, 2021, https://doi.org/10.1016/j.celrep.2021.110028; H. Mohammadi, N. Sharafkandi, M. Hemmatzadeh, et al., J Cell Physiol 233:4512–4529, 2018, https://doi.org/10.1002/jcp.26250; S. J. C. F. M. Moorlag, Y. A. Rodriguez-Rosales, J. Gillard, et al., Cell Rep 33:108387, 2021, https://doi.org/10.1016/j.celrep.2020.108387). We investigated whether a trained innate immune system with non-replicating adenoviruses could provide protection against diverse influenza virus strains. We demonstrated that replication-defective human adenoviruses can effectively train the innate immune system, conferring protective immunity in mice against multiple influenza virus strains, including H1N1, H3N2, H5N2, H7N9, and H9N2. In addition, bovine and chimpanzee adenoviruses can also activate human innate lymphoid cells (ILCs) and confer protection against challenge with influenza H3N2 virus in mice. Remarkably, this protection occurs in the complete absence of influenza-specific adaptive immune responses (influenza virus-specific hemagglutination-inhibiting antibodies, neutralizing antibodies, and influenza nucleoprotein-specific CD8 T cells). Key protective mechanisms include increased activation of ILC1, ILC2, and ILC3 populations, enhanced expression of interferon-stimulated genes (ISGs), upregulation of antiviral signaling pathways, and metabolic reprogramming of ILC subsets. Adoptive transfer experiments demonstrated that trained ILCs were sufficient to protect against influenza H1N1 infection in ILC-deficient mice. This research establishes a novel strategy for enhancing innate antiviral immunity, offering broad-spectrum protection against diverse influenza strains, a promising approach for not only pandemic preparedness but also against emerging infectious diseases. Training innate lymphoid cells through non-replicating adenoviral vectors represents a promising approach to enhancing broad-spectrum antiviral immunity, complementing traditional vaccination strategies.

IMPORTANCE

The findings represent a potential game-changer for fighting influenza, which kills hundreds of thousands of people worldwide each year despite our best vaccination efforts. Current flu vaccines often provide limited protection because they must be reformulated annually to match circulating strains, and their effectiveness varies dramatically from year to year. The scientists discovered something remarkable: common adenoviruses (which typically cause mild cold-like symptoms) can essentially “train” our immune system’s first line of defense to recognize and fight off multiple types of flu viruses simultaneously. This protection works through a completely different mechanism than traditional vaccines—it does not rely on creating specific antibodies against flu proteins. Instead, the treatment activates special immune cells called innate lymphoid cells (ILCs), which act like the body’s rapid response team. These trained cells provide broad protection against various flu strains, including dangerous bird flu variants that could cause future pandemics. The significance lies in potentially creating a universal flu protection strategy that could work against unknown future flu strains, offering hope for better pandemic preparedness and reducing seasonal flu’s devastating global impact.

Source: Journal of Virology, https://journals.asm.org/doi/10.1128/jvi.00532-25

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