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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Paralytic #rabies #outbreak mimicking #GBS in French #Amazonia

 

Abstract

Background

In the Amazonian region, vampire bats are the primary reservoir of rabies virus, causing sporadic and lethal human rabies cases that often remain unnoticed. Managing human cases in this region is challenging and further complicated by atypical clinical forms and the potential exposure to various toxic compounds, particularly among gold miners.

Methods

We carried out clinical, electrical, biological and histological analysis of concurrent cases of progressive motor neuronopathy and fatal encephalitis in a context of regular exposure to bat bites of gold miners living in a small and remote gold mine camp in Amazonia, in French Guiana, South America.

Findings

We analyzed a spatio-temporal cluster of three suspected rabies cases in 2024 with a fatal outcome, with concomitant onset of acute bilateral lower-limb paralysis without demyelination, two of which occurred presumably two weeks after a bat-bite. Electroneuromyography suggested the involvement of the anterior horn of the spinal cord, as described in furious forms of rabies. None of the cases exhibited other cardinal signs of the furious form. Confirmation of rabies was obtained for them on sera and brain biopsies collected ante- and post-mortem respectively.

Interpretation

The concurrent occurrence of disease, the axonal motor neuropathy mimicking the motor form of Guillain Barré syndrome in the context of paralytic rabies, lead to diagnostic-wandering. This underscores the importance of thinking about vampire bat rabies virus in the presence of any atypical neurological picture in patients living in exposed areas in Latin America.

Source: 

Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014149

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Life-Threatening #SARS-CoV-2–Associated #Encephalopathy and Multiorgan Failure in #Children, #Asia and #Oceania, 2022–2024

 

Abstract

SARS-CoV-2 infections in children occasionally manifest with severe neurologic signs. We report a case series of life-threatening encephalopathy associated with SARS-CoV-2 in 25 children in Australia, Japan, Singapore, and Taiwan during February 2022–January 2024. All children had severe encephalopathy develop, characterized by rapidly progressive cerebral edema, conditions known as acute shock with encephalopathy and multiorgan failure or acute fulminant cerebral edema. Among the 25 patients, 22 (88%) eventually died; 11 (44%) children died within 24 hours of hospitalization. In addition, 18 (72%) had illness manifest with shock, and 14 (56%) had multiorgan failure develop within 6 hours of neurologic onset. Serum concentrations of cytokines/chemokines including interleukin 6 and tumor necrosis factor-α were significantly higher within 24 hours of onset than for controls. SARS-CoV-2–associated encephalopathy cases such as those described here represent an emerging neurologic crisis with high mortality rate resulting from rapidly progressive brain edema and multiorgan failure.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/2/25-0549_article

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Thrombotic Events and #Stroke in the Year After #COVID19 or Other Acute Respiratory #Infection

 

Abstract

Previous studies have documented an increased risk for thrombotic events 30 days after COVID-19 infection, but less is known about this risk beyond 30 days or compared with risk after other infectious acute respiratory illnesses (ARIs). By using PCORnet data from April 1, 2022–April 30, 2023, we compared the incidences of thrombotic events in the year after COVID-19 illness with other ARI diagnoses in hospitalized and nonhospitalized patients. Overall, the risk for any thrombotic event was higher among patients with COVID-19 compared with patients with other ARIs (incidence ratio 1.63; p<0.05). Nonhospitalized patients with COVID-19 had a 73% increased risk for a thrombotic event in the year after acute illness compared with nonhospitalized patients with ARI (p<0.05). The increased risk for thrombotic events in the year after COVID-19 emphasizes the need for stroke awareness for patients and healthcare professionals.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/13/25-0630_article

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Case Report: #CJD and #diagnosis #challenges: case report and evidence synthesis

 

Abstract

Introduction

Prion diseases are mortal neurodegenerative disorders, which include Creutzfeldt-Jakob disease (CJD). Due to its heterogenous clinical presentation diagnosis uncertainties are common. In this paper we explore CJD diagnostic challenges focusing on differential diagnosis and diagnostic delays.

Methods

We report a case of a patient who was misclassified and evaluated by several medical specialties before the CJD suspicion. A systematic review of the literature of the CJD case reports focused on the timely and differential diagnosis was carried out in Medline and Embase until May 2023.

Results

Patient with diagnosis was made due to the form of presentation and clinical evolution, neuroimaging and the presence of protein 14-3-3. In systematic review, fifteen articles were selected, who reported 31 cases of CJD with problems in the timely diagnosis and incorrect initial diagnosis, the main initial differential diagnoses were psychiatry exacerbation, myelopathy, epilepsy, stroke, parkinsonism, cerebellar ataxia and autoimmune encephalitis. The most common clinical onset was psychobehavioral disturbances (apathy, confusion and sleep disturbance), extrapyramidal signs and cognitive impairment. The diagnosis delay was from one to eighteen months.

Conclusion

A discussion of the case report and the diagnostic challenges reported in the literature was made. Patients can present a wide range of symptoms. It is recommended to consider CJD for the differential diagnosis in patients with behavioral symptoms, and cognitive impairment.

Source: 

Link: https://f1000research.com/articles/14-425

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#Coinfection of #SARS-CoV-2 and #Influenza: A Catastrophic Coexistence

 

Abstract 

SARS-CoV-2 is a major global public health burden associated with significant morbidity, mortality, and complications, including respiratory, cardiovascular, neurological, and digestive disorders. COVID-19 may induce venous and arterial thromboembolic complications, including deep vein thrombosis, myocardial infarction and cerebral infarction. Simultaneous myocardial and cerebral infarction, termed cardio-cerebral infarction, is exceedingly rare. There is only limited case of concurrent cardio-cerebral infarction in patients with COVID-19. Although there is no standard treatment for the condition, antiplatelet and anticoagulation agents should be used. We emphasize the catastrophic coexistence of concurrent cardio-cerebral infarction in a patient co-infected with SARS-CoV-2 and influenza A. We described a 75-year-old woman was admitted for SARS-CoV-2 and influenza A coinfection. She received anti-viral agent treatment for the virus infection. The patient presented with right side limbs weakness and declined consciousness. The magnetic resonance imaging of brain revealed acute cerebral infarction over the left corona radiata and basal ganglion. Meanwhile, acute myocardial infarction was diagnosed using electrocardiogram and elevated cardiac enzymes. Percutaneous coronary intervention and dual-antiplatelet agents were applied for the arterial thrombosis. The patient survived and recovered with mild residual hemiparesis. In addition, this is the first reported case of concurrent cardio-cerebral infarction in patients with SARS-CoV-2 and influenza A coinfection. Coinfection with SARS-CoV-2 and influenza A is associated with more complications including thromboembolic complications. Management of concurrent cardio-cerebral infarction poses challenges, as timely intervention is critical to prevent disability or death, yet aggressive anticoagulation risks hemorrhagic complications. Optimal treatment strategies remain unclear, highlighting the need for further research. This case underscores the importance of vigilance in managing thrombotic complications in patients with SARS-CoV-2 and influenza coinfection. Despite the downgrading of the COVID-19 pandemic, clinicians must remain alert to complex presentations caused by coinfections with respiratory viruses.

Source: 

Link: https://www.dovepress.com/coinfection-of-sars-cov-2-and-influenza-a-catastrophic-coexistence-peer-reviewed-fulltext-article-IDR

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#Pediatric #Influenza-Associated #Encephalopathy and Acute Necrotizing Encephalopathy — #USA, 2024–25 Influenza Season (#CDC MMWR)

 

Summary

-- What is already known about this topic?

- Influenza-associated encephalopathy (IAE) is a rare, severe neurologic complication of influenza.

-- What is added by this report?

- During the high-severity 2024–25 influenza season, 109 U.S. pediatric IAE cases were identified; 55% of affected children were previously healthy. Thirty-seven IAE cases were subcategorized as acute necrotizing encephalopathy (ANE), a severe form of IAE characterized by rapid neurologic decline and a poor prognosis. Overall, 74% of IAE patients were admitted to an intensive care unit, and 19% died; 41% of ANE patients died. Only 16% of vaccine-eligible IAE patients had received the 2024–25 influenza vaccine.

-- What are the implications for public health practice?

- All children are at risk for severe neurologic complications of influenza. Annual influenza vaccination is recommended for all children aged ≥6 months to prevent influenza and associated complications, potentially including IAE.

Abstract

In January 2025, CDC received several reports of deaths among children aged <18 years with a severe form of influenza-associated encephalopathy (IAE) termed acute necrotizing encephalopathy (ANE). Because no national surveillance for IAE currently exists, CDC requested notification of U.S. pediatric IAE cases from clinicians and health departments during the 2024–25 influenza season, a high-severity season with a record number of pediatric influenza-associated deaths. Among 192 reports of suspected IAE submitted to CDC, 109 (57%) were categorized as IAE, 37 (34%) of which were subcategorized as ANE, and 72 (66%) as other IAE; 82 reports did not meet IAE criteria and were categorized as other influenza-associated neurologic disease. The median age of children with IAE was 5 years and 55% were previously healthy, 74% were admitted to an intensive care unit, and 19% died; 41% of children with ANE died. Only 16% of children with IAE who were vaccination-eligible had received the 2024–25 influenza vaccine. Health care providers should consider IAE in children with encephalopathy or altered level of consciousness and a recent or current febrile illness when influenza viruses are circulating. Annual influenza vaccination is recommended for all children aged ≥6 months to prevent influenza and associated complications, potentially including severe neurologic disease such as IAE and ANE.

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/mmwr/volumes/74/wr/mm7436a1.htm?s_cid=OS_mm7436a1_w

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#Influenza A Virus #Infection Impairs #Neuronal Activity in Human iPSC-Derived NGN2 Neural Co-Cultures

 

Abstract

Influenza A virus (IAV) infection is associated with a wide variety of neurological complications, of which mild complications like impaired cognitive functioning are most prominent. Even though several studies have shown that many influenza viruses can enter the CNS, the neuropathogenesis of seasonal (H3N2 and H1N1) and pandemic (pH1N1 2009) IAV infections is poorly understood. Therefore, we aimed to investigate the cellular tropism, replication efficiency and associated functional consequences using a human stem cell-derived neural co-culture model of neurons and astrocytes. All viruses were able to infect neurons in the co-culture model, although this infection did not result in efficient replication and release of progeny virus. In addition, infection did not result in visible cell death or apoptosis. However, functional analyses revealed that IAV inoculation resulted in a reduction of spontaneous neural activity and a partial reduction of neural excitability. This study shows that seasonal and pandemic IAVs can disrupt neural homeostasis, without efficient virus replication or the induction of cell death. However, these functional changes in neural activity can contribute to cognitive problems during IAV infections in the acute and potentially post-acute phase of the infection.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

ZonMw, The Dutch Organisation for knowledge and innovation in health, healthcare and well-being, https://ror.org/01yaj9a77, 91718308

The netherlands organisation for scientific research, OCENW.XS22.2.045, 024.003.001

Escmid, xx

European Union, 101084171

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.08.26.672266v1

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#COVID19-associated #neuroinflammation and #astrocyte death in the #brain linked to ORF3a-induced activation of Sur1-mediated ion channels

 

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected individuals with pre-existing medical conditions, such as neurocognitive disorders. Premorbid neurocognitive conditions compounded by COVID-19 can escalate into COVID-associated neurological complications, leading to severe illness or even death. As COVID-19 continues to persist and vaccines lose efficacy against emerging variants, individuals with neurocognitive disorders often experience prolonged symptoms that are further exacerbated by repeated breakthrough infections of highly diversified viral variants due to emergence of new viral mutations. Despite the significance of neurocognitive disorders as risk factors for COVID-19-related mortality and long COVID, the underlying causes remain largely unknown. In this study, we report a link between ORF3a expression and COVID-associated neuroinflammation and neurocytotoxicity in postmortem brain tissues from COVID-19 patients. These findings were further verified through neural cell-based in vitro and in vivo animal studies introducing ORF3a either alone or in the context of viral infection. As a membrane-associated protein, ORF3a induces upregulation of Sur1-regulated ion channels, resulting in intracellular Ca2+ influx, apoptosis, and necrosis through both NF-kB-dependent and independent proinflammatory responses in astrocytes. These findings reveal a novel clinical and mechanistic link between ORF3a and Sur1-regulated ion channels, which are highly responsive to neuroinflammatory conditions causing neurodegeneration. Additionally, we have identified a Food and Drug Administration-approved drug, glibenclamide, and a natural antiviral compound glycyrrhizin that effectively mitigates the neuropathological effects of ORF3a, underscoring the therapeutic potential and clinical significance of these findings.

Source: mBio, https://journals.asm.org/doi/full/10.1128/mbio.02012-25?af=R

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Impact of #COVID19 #vaccination #coverage on global #disability burden of #GBS

Abstract

The global burden of Guillain-Barré syndrome (GBS), an immune-mediated neuropathy, remains poorly characterized during the COVID-19 pandemic. We analyzed age-standardized years lived with disability (YLD) for GBS from 1990 to 2021 using GBD 2021 data and COVID-19 vaccination coverage from Our World in Data, focusing on 2020–2021. During the pandemic, GBS YLD rates rose dramatically, with greater increases seen in low-SDI regions, females and individuals aged 15–29 years. Higher vaccination coverage was inversely associated with GBS disability burden, exhibiting a non-linear protective effect at moderate to high coverage levels. Causal mediation analysis indicated that 44.6% of this association was mediated by reductions in COVID-19 incidence, highlighting both direct and indirect neuroprotective benefits of vaccination programs. These results underscore the importance of sustaining and expanding the vaccine rollout to mitigate the secondary neurological burden associated with emerging infections.

Source: npj Vaccines, https://www.nature.com/articles/s41541-025-01239-1

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#SARS-CoV-2 #Infection of the #CNS: A Case Report

Abstract

Central nervous system (CNS) infections caused by SARS-CoV-2 are uncommon. This case report describes the clinical progression of a 92-year-old female who developed a persistent neuroinfection associated with SARS-CoV-2. The patient initially presented with progressive fatigue, catarrhal symptoms, and a fever (38.6 °C). Initial laboratory findings revealed hypoxemia (O2 saturation 79.8%), acidosis (pH 7.3), an elevated C-reactive protein (CRP) level of 14.8 mg/L, and a high D-dimer level (2.15 µg/mL). Nasopharyngeal (NP) antigen and RT-PCR tests confirmed SARS-CoV-2 infection, and an NP swab also detected penicillin- and ampicillin-resistant Staphylococcus aureus. She was admitted for conservative management, including oxygen supplementation, IV fluids, and prophylactic anticoagulation. Subsequently, she developed neurological symptoms—lethargy, discoordination, and impaired communication—without signs of meningism. Cerebrospinal fluid (CSF) analysis identified SARS-CoV-2 RNA (Ct = 29) on RT-PCR, while bacterial cultures remained negative. Treatment was intensified to include 10% mannitol, dexamethasone, and empiric ceftriaxone. Despite these interventions, the patient remained somnolent, with a Glasgow Coma Scale (GCS) score of 10. Upon discharge, her GCS had improved to 14; however, she continued to experience lethargy and cognitive issues, commonly described as “brain fog”. Inflammatory markers remained elevated (CRP 23 mg/L) and repeat RT-PCR of CSF confirmed a persistent SARS-CoV-2 presence (Ct = 31). This case underscores the potential for SARS-CoV-2 to cause prolonged CNS involvement, leading to persistent neurological impairment despite standard therapy. Further research is essential to clarify the pathophysiology of and determine optimal management for SARS-CoV-2 neuroinfections.

Source: Viruses, https://www.mdpi.com/1999-4915/16/12/1962

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