Tag: Guillain Barré

Biomarkers of post-acute infection syndrome: a systematic literature review

Abstract:

Background: Post-acute infection syndrome (PAIS) remained underrecognized before the COVID-19 pandemic, which further increased exposure by introducing a novel global cause. The global burden of post-acute COVID syndrome (PACS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) alone is estimated at several tens of millions affected worldwide. Biomarker discovery is central to improving PAIS diagnosis and may provide therapeutic targets. This review summarizes current knowledge on biomarkers for PAIS, including PACS and ME/CFS.

Methods: A systematic literature search was conducted in PubMed and Web of Science. Inclusion criteria were: (1) studies including PAIS patients; (2) reporting laboratory or omics biomarkers; and (3) investigating biomarkers or pathomechanisms of PAIS. Although Guillain-Barré syndrome (GBS) is not PAIS, we have included it as a separate mechanistic comparator due to its prevalence in search results and its clinical and immunological similarities to PAIS.

Results: A total of 142 studies analyzing PAIS biomarkers were included. GBS was analyzed separately and later compared with the other results. Overall, the reviewed studies employed heterogeneous approaches. While similar types of data were frequently investigated, analytical methods varied and often focused only on a subset of molecules. The results indicate that amino acid, energy, and lipid metabolism, microbiome, mitochondrial stress, and miRNA networks are affected. All pathways are connected via NF-κB.

Discussion: PAIS is a multisystem disorder rooted in persistent immune activation, metabolic reprogramming, and systemic inflammation, driven not by active viral infection, but by dysregulated host responses. The NF-κB pathway serves as a unifying hub, connecting molecular, cellular, and clinical phenotypes. Our framework enables a shift from symptom-based to mechanism-based classification, paving the way for biologically grounded interventions.

Conclusion: This review synthesizes a broad spectrum of biomarkers in PAIS, integrating findings across pathogens and molecular levels rather than restricting to individual conditions or symptom clusters. This study highlights the differences and commonalities among pathogens and diseases that lead to post-acute sequelae, fills a critical knowledge gap, and provides a foundation for future research and clinical practice. Future studies incorporating multi-omics approaches, longitudinal designs, and larger patient cohorts are needed to validate specific biomarkers and advance the understanding of PAIS.

Source: Wendt K, Schieck M, Gille C, Marschollek M, Illig T, Wolff D, Nee S. Biomarkers of post-acute infection syndrome: a systematic literature review. Front Immunol. 2026 Jun 30;17:1741761. doi: 10.3389/fimmu.2026.1741761. PMID: 42454043; PMCID: PMC13365053. https://pmc.ncbi.nlm.nih.gov/articles/PMC13365053/ (Full text)

Pathophysiology, diagnosis, and management of neuroinflammation in covid-19

Abstract:

Although neurological complications of SARS-CoV-2 infection are relatively rare, their potential long term morbidity and mortality have a significant impact, given the large numbers of infected patients. Covid-19 is now in the differential diagnosis of a number of common neurological syndromes including encephalopathy, encephalitis, acute demyelinating encephalomyelitis, stroke, and Guillain-Barré syndrome.

Physicians should be aware of the pathophysiology underlying these presentations to diagnose and treat patients rapidly and appropriately. Although good evidence has been found for neurovirulence, the neuroinvasive and neurotropic potential of SARS-CoV-2 is limited. The pathophysiology of most complications is immune mediated and vascular, or both. A significant proportion of patients have developed long covid, which can include neuropsychiatric presentations. The mechanisms of long covid remain unclear. The longer term consequences of infection with covid-19 on the brain, particularly in terms of neurodegeneration, will only become apparent with time and long term follow-up.

Source: Brown R L, Benjamin L, Lunn M P, Bharucha T, Zandi M S, Hoskote C et al. Pathophysiology, diagnosis, and management of neuroinflammation in covid-19 BMJ 2023; 382 :e073923 doi:10.1136/bmj-2022-073923 https://www.bmj.com/content/382/bmj-2022-073923.abstract (Full text available as PDF file)

Small fiber neuropathy underlying dysautonomia in COVID-19 and in post-SARS-CoV-2 vaccination and long-COVID syndromes

Letter:

We eagerly read the excellent editorial by Gemignani and the corresponding original article by Abrams et al. about the suspected involvement of small fibers (small fiber neuropathy [SFN]) in acute severe, acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and in long-coronavirus disease (COVID) syndrome.1, 2 It was speculated that at least some of the clinical manifestations of long-COVID syndrome could be attributed to involvement of small nerve fibers by the viral infection. The authors believe that studies are needed that investigate the role of autonomic dysfunction in long-COVID syndrome and the prevalence of SFN by means of the 13-item SFN symptom inventory questionnaire. The papers are appealing but raise some concerns that require discussion.

I do not agree with the notion that long-COVID syndrome is the same as post-COVID syndrome.1 Acute COVID-19 usually lasts one to 4 wk. Subacute COVID-19 lasts 5 to 12 wk. When clinical manifestations of COVID-19 persist beyond 12 wk, the condition is termed post-COVID syndrome. Both subacute COVID-19 and post-COVID syndrome are included under the overarching term long-COVID-syndrome. Differentiating long-COVID syndrome from post-COVID-syndrome is crucial for their management and for assessing long-term outcomes.

An issue not addressed in the paper is Guillain-Barre syndrome (GBS) due to an infection with SARS-CoV-2.3 There is ample evidence that the immune response to the virus can trigger autoimmune reactions, including those that are involved in the development of GBS. There is evidence accumulating that mRNA- and vector-based anti-SARS-CoV-2 vaccines can trigger the development of GBS.4 GBS can affect not only motor and sensory fibers, but also peripheral autonomic fibers, particularly in the GBS subtype of acute motor and sensory axonal neuropathy (AMSAN). There is a subtype of GBS that may exclusively affect autonomic fibers and present with pure dysautonomia.5 Because GBS may be mild, it can go unrecognized; because patients often have a long recovery time, autonomic manifestations in long COVID syndrome could be explained by incomplete recovery from autonomic involvement in abortive GBS.

Not addressed in the articles is the involvement of the central autonomic nervous system (ANS). There are several reports demonstrating that a SARS-CoV-2 infection can be complicated by hypophysitis.6 Furthermore, patients with a pre-existing pituitary micro- or macro-adenoma have an increased risk of pituitary apoplexy during SARS-CoV-2 infection.7 Accordingly, the hypophysial-pituitary-adrenergic axis can be impaired,8 thus leading to autonomic dysfunction.

Autonomic dysfunction may not always be recognized by those involved in the management of COVID-19 patients. Thus, patients with SARS-CoV-2 infection are often not investigated sufficiently for their symptoms of autonomic dysfunction, such as insomnia, fatigue, cognitive impairment, hypersensitivity to light, blurred vision, dry eyes or mouth, drooling, palpitations, syncope, orthostatic dizziness, hot flashes, dysphagia, bowel or bladder dysfunction, sexual dysfunction, changes in skin, hair, and nails, or abnormalities of sweating. Studies that may be performed to assess ANS involvement are a contrast-enhanced magnetic resonance imaging (MRI) of the pituitary gland, determination of releasing factors, pituitary stimulating hormones, and hormones of peripheral endocrine organs, and diagnostic testing for involvement of the peripheral ANS. Several of the latter tests are not widely available and their sensitivity and specificity may be low if portions of the peripheral ANS are tested that are not affected.

Not addressed was the role of anti-COVID-19 drugs in the development of SFN. There is increasing evidence that some of the compounds administered to infected patients are neurotoxic and can be responsible for polyneuropathy. Some of these compounds, such as lopinavir, ritonavir, daptomycin, and linezolid, may also damage autonomic fibers.

I agree that there is a need to investigate the involvement of the central and peripheral ANS in some patients with acute SARS-CoV-2 infections or long-COVID syndrome. Such patients should be investigated not only by use of questionnaires and the Quantitative Sudomotor Axon Reflex Test (QSART) but particularly by quantitative sensory testing (QST), micro-neurography of C-fibers of the superficial peroneal nerve, sensory stimulation tests, the deep breathing test, the Valsalva maneuver, tilt testing, cerebral blood flow velocity measurements, pain-related evoked potentials (PREP), laser speckle contact analysis (LASCA), laser Doppler flowmetry, laser Doppler imaging, contact heat-evoked potentials (CHEP), corneal confocal microscopy (CCM), and proximal or distal skin biopsy stained with protein gene product (PGP) 9.5. Furthermore, hormone levels should be determined and autopsy of COVID-19 patients should include histological investigations of central and peripheral autonomic pathways.

Source: Finsterer J. Small fiber neuropathy underlying dysautonomia in COVID-19 and in post-SARS-CoV-2 vaccination and long-COVID syndromes. Muscle Nerve. 2022 Apr 6. doi: 10.1002/mus.27554. Epub ahead of print. PMID: 35385125.  https://onlinelibrary.wiley.com/doi/10.1002/mus.27554 (Full text)

Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002-2012

Abstract:

BACKGROUND: In Finland a vaccination programme against human papillomavirus (HPV) was introduced in November 2013 for girls aged 11-12 years with a catchup for girls 13-15 years. Allegations that HPV vaccine is causing Guillain Barré syndrome (GBS) and non-specific diagnostic entities, such as chronic fatigue syndrome/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS), continue to surface. We examined population register-based incidence rates of CFS/SEID, GBS and POTS to provide baseline data for future HPV vaccine safety evaluations.

METHODS: First diagnosis of CFS/SEID, GBS and POTS in girls aged 11-15 years were obtained from the National Hospital Discharge Register during 2002-2012. We considered the following ICD-10 codes: G93.3 for CFS; G61.0 for GBS and G90.9, G90.8, G93.3, I49.8 for POTS. We calculated incidence rates per 100,000 person-years with 95% confidence intervals (CI).

RESULTS: In total, 9 CFS/SEID, 19 GBS and 72 POTS cases were identified. The overall incidence rate was 0.53/100,000 (95% CI; 0.27-1.01) for CFS/SEID, 1.11 (95% CI; 0.71-1.74) for GBS and 4.21 (95%CI; 3.34-5.30) for POTS. Significant relative increase in annual incidence rate with a peak in 2012 was observed in CFS/SEID (33% (95% CI; 3.0-70.3: p=0.029) and POTS (16.5% (95% CI; 7.8-25.9: p<0.05), but not in GBS (5.4% (95% CI; -8.4-21.3: p=0.460).

CONCLUSIONS: Our findings provide baseline estimates of CFS/SEID, GBS and POTS incidences in Finland. However, rates based on register data should be interpreted with caution, especially for non-specific diagnostic entities for which internationally and even nationally agreed criteria are still being discussed. To assess the associations with HPV vaccine, methods using register linkage for cohort and self-controlled case series should be explored in addition to factors contributing to patients seeking care, treating physicians setting the diagnoses, and their preference of using of codes for these clinical entities.

Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Source: Skufca J, Ollgren J, Ruokokoski E, Lyytikäinen O, Nohynek H. Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002-2012. Papillomavirus Res. 2017 Jun;3:91-96. doi: 10.1016/j.pvr.2017.03.001. Epub 2017 Mar 16. http://www.sciencedirect.com/science/article/pii/S2405852116300696?via%3Dihub (Full article)