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Tag: autoimmunity

Long COVID-19 and Insulin Autoimmune Syndrome: A Case Report

Abstract:

Purpose: To describe a case report of a patient with symptoms associated with metabolic alterations 1 month after having COVID-19.

Methods: Laboratory tests, clinical evaluations, and body composition assessments were performed by specialists.

Findings: The patient presented excessive sweating, hot flashes, dizziness, blurred vision, and seizure. Laboratory tests indicated low glucose levels after convulsions (50, 42.7, and 55 mg/dL), high insulin levels (basal, 638 µIU/mL; 2-hour, >1000 µU/mL), and positivity for anti-insulin antibodies. The patient was diagnosed with insulin autoimmune syndrome. Treatment with azathioprine and nutritional recommendations improved remission.

Implications: SARS-CoV-2 infection or vaccination might induce insulin tolerance failure.

Source: Corona-Meraz FI, Quintero-Castillo BP, Hernández-Palma LA, Machado-Sulbaran AC. Long COVID-19 and Insulin Autoimmune Syndrome: A Case Report. Clin Ther. 2023 Jul 29:S0149-2918(23)00250-3. doi: 10.1016/j.clinthera.2023.06.026. Epub ahead of print. PMID: 37524570. https://pubmed.ncbi.nlm.nih.gov/37524570/

Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID

Abstract:

While immunologic correlates of COVID-19 have been widely reported, their associations with post-acute sequelae of COVID-19 (PASC) remain less clear. Due to the wide array of PASC presentations, understanding if specific disease features associate with discrete immune processes and therapeutic opportunities is important.

Here we profile patients in the recovery phase of COVID-19 via proteomics screening and machine learning to find signatures of ongoing antiviral B cell development, immune-mediated fibrosis, and markers of cell death in PASC patients but not in controls with uncomplicated recovery. Plasma and immune cell profiling further allow the stratification of PASC into inflammatory and non-inflammatory types.

Inflammatory PASC, identifiable through a refined set of 12 blood markers, displays evidence of ongoing neutrophil activity, B cell memory alterations, and building autoreactivity more than a year post COVID-19. Our work thus helps refine PASC categorization to aid in both therapeutic targeting and epidemiological investigation of PASC.

Source: Woodruff MC, Bonham KS, Anam FA, Walker TA, Faliti CE, Ishii Y, Kaminski CY, Ruunstrom MC, Cooper KR, Truong AD, Dixit AN, Han JE, Ramonell RP, Haddad NS, Rudolph ME, Yalavarthi S, Betin V, Natoli T, Navaz S, Jenks SA, Zuo Y, Knight JS, Khosroshahi A, Lee FE, Sanz I. Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID. Nat Commun. 2023 Jul 14;14(1):4201. doi: 10.1038/s41467-023-40012-7. PMID: 37452024; PMCID: PMC10349085. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349085/ (Full text)

A Molecular Biomarker-Based Triage Approach for Targeted Treatment of Post-COVID-19 Syndrome Patients with Persistent Neurological or Neuropsychiatric Symptoms

Abstract:

Approximately 30% of COVID-19 cases may experience chronic symptoms, known as post-COVID-19 syndrome (PCS). Common PCS symptoms can include fatigue, cognitive impairment, and persistent physical, neurological, and neuropsychiatric complaints.

To improve healthcare and management of the current and future pandemics, we highlight the need for establishing interdisciplinary post-viral outpatient clinics comprised of specialists in fields such as psychiatry, psychotherapy, neurology, cardiology, pneumology, and immunology. In this way, PCS patients with a high health burden can receive modern diagnostics and targeted therapeutic recommendations. A key objective is to distinguish the “sick recovered” from the “healthy recovered.”

Our hypothesis is that there is a PCS subgroup with autoimmune-mediated systemic and brain-vascular dysregulation, which may lead to circulatory disorders, fatigue, cognitive impairment, depression, and anxiety. This can be clarified using a combination of specific antibody diagnostics and precise clinical, psychological, and apparative testing.

Source: Guest PC, Neyazi A, Braun-Dullaeus RC, Müller P, Schreiber J, Haghikia A, Vasilevska V, Steiner J. A Molecular Biomarker-Based Triage Approach for Targeted Treatment of Post-COVID-19 Syndrome Patients with Persistent Neurological or Neuropsychiatric Symptoms. Adv Exp Med Biol. 2023;1412:97-115. doi: 10.1007/978-3-031-28012-2_5. PMID: 37378763. https://pubmed.ncbi.nlm.nih.gov/37378763/

Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID

Abstract:

Long COVID patients who experienced severe acute SARS-CoV-2 infection can present with humoral autoimmunity. However, whether mild SARS-CoV-2 infection increases autoantibody responses and whether vaccination can decrease autoimmunity in long COVID patients is unknown.

Here, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with systemic lupus erythematosus (SLE) and inflammatory myopathies in long COVID patients with persistent neurologic symptoms to a greater extent than COVID convalescent controls at 8 months post-infection. Furthermore, high titers of SLE-associated autoantibodies in long COVID patients are associated with impaired cognitive performance and greater symptom severity, and subsequent vaccination/booster does not decrease autoantibody titers.

In summary, we found that mild SARS-CoV-2 infection can induce persistent humoral autoimmunity in both long COVID patients and healthy COVID convalescents, suggesting that a reappraisal of vaccination and mitigation strategies is warranted.

Source: Visvabharathy L, Zhu C, Orban ZS, Yarnoff K, Palacio N, Jimenez M, Lim PH, Penaloza-MacMaster P, Koralnik IJ. Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID. medRxiv [Preprint]. 2023 Apr 12:2023.04.07.23288243. doi: 10.1101/2023.04.07.23288243. PMID: 37090595; PMCID: PMC10120795. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120795/ (Full text)

Investigating antibody reactivity to the intestinal microbiome in severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic disease of unknown aetiology that is characterised by disabling chronic fatigue and involves both the immune and gastrointestinal (GI) systems. Patients display alterations in GI microbiome with a significant proportion experiencing GI discomfort and pain and elevated blood biomarkers for altered intestinal permeability compared with healthy individuals.

To investigate a possible GI origin of ME/CFS we designed a feasibility study to test the hypothesis that ME/CFS pathogenesis is a consequence of increased intestinal permeability that results in microbial translocation and a breakdown in immune tolerance leading to generation of antibodies reactive to indigenous intestinal microbes. Secretory IgA and serum IgG levels and reactivity to intestinal microbes were assessed in five pairs of severe ME/CFS patients and matched same-household healthy controls. For profiling serum IgG we developed IgG-Seq which combines flow-cytometry based bacterial cell sorting and metagenomics to detect mucosal IgG reactivity to the microbiome.

We uncovered evidence for immune dysfunction in severe ME/CFS patients that was characterised by reduced capacity and reactivity of serum IgG to stool microbes, irrespective of their source. This study provides the rationale for additional studies in larger cohorts of ME/CFS patients to further explore immune-microbiome interactions.

Source: Katharine A. Seton, Marianne Defernez, Andrea Telatin, Sumeet K. Tiwari, George M. Savva, Antonietta Hayhoe, Alistair Noble, Ana Carvalho, Steve James, Amolak Bansal, Thomas Wileman, Simon R. Carding. Investigating antibody reactivity to the intestinal microbiome in severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). medRxiv 2023.05.21.23290299; doi: https://doi.org/10.1101/2023.05.21.23290299 https://www.medrxiv.org/content/10.1101/2023.05.21.23290299v1.full-text (Full text)

Long-Term Adverse Effects of Mild COVID-19 Disease on Arterial Stiffness, and Systemic and Central Hemodynamics: A Pre-Post Study

Abstract:

COVID-19-associated vascular disease complications are primarily associated with endothelial dysfunction; however, the consequences of disease on vascular structure and function, particularly in the long term (>7 weeks post-infection), remain unexplored. Individual pre- and post-infection changes in arterial stiffness as well as central and systemic hemodynamic parameters were measured in patients diagnosed with mild COVID-19.
As part of in-laboratory observational studies, baseline measurements were taken up to two years before, whereas the post-infection measurements were made 2–3 months after the onset of COVID-19. We used the same measurement protocol throughout the study as well as linear and mixed-effects regression models to analyze the data. Patients (N = 32) were predominantly healthy and young (mean age ± SD: 36.6 ± 12.6). We found that various parameters of arterial stiffness and central hemodynamics—cfPWV, AIx@HR75, and cDBP as well as DBP and MAP—responded to a mild COVID-19 disease.
The magnitude of these responses was dependent on the time since the onset of COVID-19 as well as age (pregression_models ≤ 0.013). In fact, mixed-effects models predicted a clinically significant progression of vascular impairment within the period of 2–3 months following infection (change in cfPWV by +1.4 m/s, +15% in AIx@HR75, approximately +8 mmHg in DBP, cDBP, and MAP).
The results point toward the existence of a widespread and long-lasting pathological process in the vasculature following mild COVID-19 disease, with heterogeneous individual responses, some of which may be triggered by an autoimmune response to COVID-19.
Source: Podrug M, Koren P, Dražić Maras E, Podrug J, Čulić V, Perissiou M, Bruno RM, Mudnić I, Boban M, Jerončić A. Long-Term Adverse Effects of Mild COVID-19 Disease on Arterial Stiffness, and Systemic and Central Hemodynamics: A Pre-Post Study. Journal of Clinical Medicine. 2023; 12(6):2123. https://doi.org/10.3390/jcm12062123 https://www.mdpi.com/2077-0383/12/6/2123 (Full text)

Risk of autoimmune diseases in patients with COVID-19: A retrospective cohort study

Abstract:

Background: There are a growing number of case reports of various autoimmune diseases occurring after COVID-19, yet there is no large-scale population-based evidence to support this potential association. This study provides a closer insight into the association between COVID-19 and autoimmune diseases and reveals discrepancies across sex, age, and race of participants.

Methods: This is a retrospective cohort study based on the TriNetX U.S. Collaborative Network. In the test-negative design, cases were participants with positive polymerase chain reaction (PCR) test results for SARS-CoV-2, while controls were participants who tested negative and were not diagnosed with COVID-19 throughout the follow-up period. Patients with COVID-19 and controls were propensity score-matched (1: 1) for age, sex, race, adverse socioeconomic status, lifestyle-related variables, and comorbidities. The primary endpoint is the incidence of newly recorded autoimmune diseases. Adjusted hazard ratios (aHRs) and 95% confident intervals (CIs) of autoimmune diseases were calculated between propensity score-matched groups with the use of Cox proportional-hazards regression models.

Findings: Between January 1st, 2020 and December 31st, 2021, 3,814,479 participants were included in the study (888,463 cases and 2,926,016 controls). After matching, the COVID-19 cohort exhibited significantly higher risks of rheumatoid arthritis (aHR:2.98, 95% CI:2.78-3.20), ankylosing spondylitis (aHR:3.21, 95% CI:2.50-4.13), systemic lupus erythematosus (aHR:2.99, 95% CI:2.68-3.34), dermatopolymyositis (aHR:1.96, 95% CI:1.47-2.61), systemic sclerosis (aHR:2.58, 95% CI:2.02-3.28), Sjögren’s syndrome (aHR:2.62, 95% CI:2.29-3.00), mixed connective tissue disease (aHR:3.14, 95% CI:2.26-4.36), Behçet’s disease (aHR:2.32, 95% CI:1.38-3.89), polymyalgia rheumatica (aHR:2.90, 95% CI:2.36-3.57), vasculitis (aHR:1.96, 95% CI:1.74-2.20), psoriasis (aHR:2.91, 95% CI:2.67-3.17), inflammatory bowel disease (aHR:1.78, 95%CI:1.72-1.84), celiac disease (aHR:2.68, 95% CI:2.51-2.85), type 1 diabetes mellitus (aHR:2.68, 95%CI:2.51-2.85) and mortality (aHR:1.20, 95% CI:1.16-1.24).

Interpretation: COVID-19 is associated with a different degree of risk for various autoimmune diseases. Given the large sample size and relatively modest effects these findings should be replicated in an independent dataset. Further research is needed to better understand the underlying mechanisms.

Source: Chang R, Yen-Ting Chen T, Wang SI, Hung YM, Chen HY, Wei CJ. Risk of autoimmune diseases in patients with COVID-19: A retrospective cohort study. EClinicalMedicine. 2023 Feb;56:101783. doi: 10.1016/j.eclinm.2022.101783. Epub 2023 Jan 10. PMID: 36643619; PMCID: PMC9830133. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9830133/ (Full text)

High risk of autoimmune diseases after COVID-19

The full picture of post-COVID-19 autoimmune diseases and their prevalence is lacking despite numerous case reports and small series. Two studies that use large cohorts now highlight that SARS-CoV-2 infection is linked to a substantially increased risk of developing a diverse spectrum of new-onset autoimmune diseases.

Refers to: Chang, R. et al. Risk of autoimmune diseases in patients with COVID-19: a retrospective cohort study. eClinicalMedicine 56, 101783 (2023).

The triggering of autoimmune conditions by viral infections has been of interest to the scientific community for decades. The COVID-19 pandemic provides a unique opportunity to understand this link and the underlying pathogenesis. SARS-CoV-2 infection leads to a spectrum of symptoms in the host, with respiratory symptoms dominating the clinical picture. SARS-CoV-2 was originally thought to mostly cause respiratory illness, with comparisons being made to common influenza.

However, in a steep learning curve, the spectrum of SARS-CoV-2 infection was observed to range from self-limiting mild infection to critical respiratory distress, with symptoms including fever, cough, myalgia, fatigue and dyspnea1. Severe COVID-19 cases have demonstrated a substantial inflammatory response with pro-inflammatory cytokines and chemokines that stimulate pulmonary inflammation1.

As the burden of COVID-19 cases increases worldwide, so does our understanding of the condition. Owing to worldwide vaccination efforts, mortality due to COVID-19 has been decreasing, but we continue to witness considerable morbidity and increased rates of post-COVID-19 conditions and in particular, new-onset autoimmune and inflammatory diseases in individuals who have had COVID-19. The range and incidence of these post-COVID-19 disorders have now been highlighted in two large retrospective cohort studies2,3.

Source: Sharma, C., Bayry, J. High risk of autoimmune diseases after COVID-19. Nat Rev Rheumatol (2023). https://doi.org/10.1038/s41584-023-00964-y (Full text)

A review of cytokine-based pathophysiology of Long COVID symptoms

Abstract:

The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production.

In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with “brain fog,” arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines.

There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS.

Source: Low RN, Low RJ, Akrami A. A review of cytokine-based pathophysiology of Long COVID symptoms. Front Med (Lausanne). 2023 Mar 31;10:1011936. doi: 10.3389/fmed.2023.1011936. PMID: 37064029; PMCID: PMC10103649. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103649/ (Full text)

Long COVID in autoimmune rheumatic diseases

Abstract:

Consequences of Corona Virus Disease-19 (COVID-19) in patients with rheumatic diseases (RDs) are clinically diverse. SARS-CoV-2 infection has been associated with various autoimmune and rheumatic manifestations over the past three years. Emerging evidence points to the possibility of Long COVID predisposition in rheumatic patients due to the changes in immune regulatory response. The aim of this article was to overview data on the pathobiology of Long COVID in patients with RDs.

Related risk factors, clinical characteristics, and prognosis of Long COVID in RDs were analyzed. Relevant articles were retrieved from Medline/PubMed, Scopus, and Directory of Open Access Journals (DOAJ). Diverse mechanisms of viral persistence, chronic low-grade inflammation, lasting production of autoantibodies, endotheliopathy, vascular complications, and permanent tissue damage have been described in association with Long COVID. Patients with RDs who survive COVID-19 often experience severe complications due to the immune disbalance resulting in multiple organ damage. Regular monitoring and treatment are warranted in view of the accumulating evidence.

Source: Fedorchenko Y, Zimba O. Long COVID in autoimmune rheumatic diseases. Rheumatol Int. 2023 Mar 30:1–11. doi: 10.1007/s00296-023-05319-0. Epub ahead of print. PMID: 36995436; PMCID: PMC10061411. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10061411/ (Full text)