Tag: autoimmunity

Autoimmunity is a hallmark of post-COVID syndrome

Abstract:

Autoimmunity has emerged as a characteristic of the post-COVID syndrome (PCS), which may be related to sex. In order to further investigate the relationship between SARS-CoV-2 and autoimmunity in PCS, a clinical and serological assessment on 100 patients was done. Serum antibody profiles against self-antigens and infectious agents were evaluated by an antigen array chip for 116 IgG and 104 IgM antibodies.

Thirty pre-pandemic healthy individuals were included as a control group. The median age of patients was 49 years (IQR: 37.8 to 55.3). There were 47 males. The median post-COVID time was 219 (IQR: 143 to 258) days. Latent autoimmunity and polyautoimmunity were found in 83% and 62% of patients, respectively.

Three patients developed an overt autoimmune disease. IgG antibodies against IL-2, CD8B, and thyroglobulin were found in more than 10% of the patients. Other IgG autoantibodies, such as anti-interferons, were positive in 5-10% of patients. Anti-SARS-CoV-2 IgG antibodies were found in > 85% of patients and were positively correlated with autoantibodies, age, and body mass index (BMI). Few autoantibodies were influenced by age and BMI. There was no effect of gender on the over- or under-expression of autoantibodies. IgG anti-IFN-λ antibodies were associated with the persistence of respiratory symptoms.

In summary, autoimmunity is characteristic of PCS, and latent autoimmunity correlates with humoral response to SARS-CoV-2.

Source: Rojas M, Rodríguez Y, Acosta-Ampudia Y, Monsalve DM, Zhu C, Li QZ, Ramírez-Santana C, Anaya JM. Autoimmunity is a hallmark of post-COVID syndrome. J Transl Med. 2022 Mar 16;20(1):129. doi: 10.1186/s12967-022-03328-4. PMID: 35296346; PMCID: PMC8924736. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924736/ (Full text)

Long COVID from rheumatology perspective: a simple mimicker or promoter of autoimmunity?

Dear editor,

We have read with great interest the review article by Sapkota et al. which has been recently published in the Clinical Rheumatology journal dealing with long COVID []. In this paper, the authors reported the symptoms and immunological findings of patients who were infected from severe acute respiratory syndrome coronovirus-2 (SARS-CoV-2). These symptoms and laboratory features share similarities with those of patients suffering from autoimmune rheumatic diseases (ARDs). They concluded that long COVID is a mimicker of ARDs and needs to be excluded to ensure a correct diagnosis [].

Recently, we reported a patient who contracted SARS-CoV-2 infection and developed an erosive seronegative arthritis six months after infection []. Musculoskeletal, cutaneous, and other systemic manifestations, along with the presence of autoantibodies, are frequently observed in these patients. On the other hand, SARS-CoV-2 may trigger autoimmune responses and the development of de-novo manifestations of ARDs, as in our patient []. The pathogenesis of these phenomena is not well defined. One hypothesis implies the presence of autoantibodies against interferon (IFN) type-I, or inborn errors in the type-I IFN immunity [, ]. Another hypothesis is that SARS-CoV-2 might trigger autoimmune responses through molecular mimicry []. Several viruses have been implicated as possible etiological factors for the development of ARDs, mostly systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and others. Between viruses Epstein-Barr virus (EBV) is implicated in the pathogenesis of the above disorders [, ]. Indeed, EBV can trigger immune responses through molecular mimicry and is a polyclonal activator of B-cells and increases the production of rheumatoid factor (RF). Several studies suggested that molecular mimicry is a possible mechanism responsible for the development of ARDs in SARS-CoV-2 infection [, ]. Thus, SARS-CoV-2 may trigger autoimmunity and the possible development of the de novo manifestations of ARDs.

Read the full article HERE.

Source: Drosos AA, Pelechas E, Voulgari PV. Long COVID from rheumatology perspective: a simple mimicker or promoter of autoimmunity? Clin Rheumatol. 2022 Feb 11:1–2. doi: 10.1007/s10067-022-06092-4. Epub ahead of print. PMID: 35147823; PMCID: PMC8831874. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831874/ (Full text)

Persistent Autoimmune Activation and Proinflammatory State in Post-COVID Syndrome

Abstract:

Background: The immunopathological pathways enabling post-COVID syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition.

Methods: Thirty-three patients were included for longitudinal clinical and autoantibody analyses of whom 12 patients were assessed for cytokines and lymphocyte populations. Patients were followed during 7-11 months after acute COVID-19. Autoimmune profile and immunological status were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry.

Results: Latent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by upregulated IFN-α, TNF-α, G-CSF, IL-17A, IL-6, IL-1β, and IL-13, whereas IP-10 was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of IgG S1-SARS-CoV-2 antibodies remained elevated over time.

Discussion: The clinical manifestations of PCS are associated with the persistence of a proinflammatory, and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.

Source: Acosta-Ampudia Y, Monsalve DM, Rojas M, Rodríguez Y, Zapata E, Ramírez-Santana C, Anaya JM. Persistent Autoimmune Activation and Proinflammatory State in Post-COVID Syndrome. J Infect Dis. 2022 Jan 25:jiac017. doi: 10.1093/infdis/jiac017. Epub ahead of print. PMID: 35079804. https://pubmed.ncbi.nlm.nih.gov/35079804/

Intravenous immunoglobulin as an important adjunct in the prevention and therapy of coronavirus 2019 disease

Abstract:

The coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenged globally with its morbidity and mortality. A small percentage of affected patients (20%) progress into the second stage of the disease clinically presenting with severe or fatal involvement of lung, heart and vascular system, all contributing to multiple-organ failure. The so-called ‘cytokines storm’ is considered the pathogenic basis of severe disease and it is a target for treatment with corticosteroids, immunotherapies and intravenous immunoglobulin (IVIg).

We provide an overview of the role of IVIg in the therapy of adult patients with COVID-19 disease. After discussing the possible underlying mechanisms of IVIg immunomodulation in COVID-19 disease, we review the studies in which IVIg was employed. Considering the latest evidence that show a link between new coronavirus and autoimmunity, we also discuss the use of IVIg in COVID-19 and anti-SARS-CoV-2 vaccination related autoimmune diseases and the post-COVID-19 syndrome.

The benefit of high-dose IVIg is evident in almost all studies with a rapid response, a reduction in mortality and improved pulmonary function in critically ill COVID-19 patients. It seems that an early administration of IVIg is crucial for a successful outcome. Studies’ limitations are represented by the small number of patients, the lack of control groups in some and the heterogeneity of included patients. IVIg treatment can reduce the stay in ICU and the demand for mechanical ventilation, thus contributing to attenuate the burden of the disease.

Source: Danieli MG, Piga MA, Paladini A, Longhi E, Mezzanotte C, Moroncini G, Shoenfeld Y. Intravenous immunoglobulin as an important adjunct in the prevention and therapy of coronavirus 2019 disease. Scand J Immunol. 2021 Nov;94(5):e13101. doi: 10.1111/sji.13101. Epub 2021 Sep 16. PMID: 34940980; PMCID: PMC8646640. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8646640/ (Full text)

Covid-19: Long covid symptoms among hospital inpatients show little improvement after a year, data suggest

People admitted to hospital with covid-19 who reported “long covid” symptoms five months after discharge had made only limited improvement after a full year, preliminary data from the PHOSP-COVID study show.

Researchers said that their results, released as a preprint on 16 December,1 showed that patients who experienced the most severe symptoms also had raised levels of substances associated with whole body inflammation and tissue damage and repair, suggesting autoimmune involvement.

The study, led by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, is following up 2230 adults admitted to hospital with covid-19. At five months after discharge only 2.5 in 10 people felt fully recovered.2 This was largely unchanged after 12 months, at less than 3 in 10 patients, in the 807 people assessed so far.

Chris Brightling, professor of respiratory medicine at the University of Leicester and chief investigator for the study, said, “People who were hospitalised and went on to develop long covid are not getting substantially better a year after they were discharged from hospital.

“Many patients in our study had not fully recovered at five months, and most of these reported little positive change in their health condition at one year.”

Rachael Evans, associate professor at the University of Leicester and respiratory consultant at Leicester’s Hospitals, who is the paper’s lead author, said, “Healthcare professionals will need to proactively continue assessing their patients for some time to come in order to identify their ongoing healthcare needs and provide support.

“We urgently need healthcare packages and medicines that target the potentially treatable traits of long covid to help people feel better and get back to their normal lives. Without these, long covid has the potential to become highly prevalent as a new long term condition.”

Ongoing inflammatory process

The most common long covid symptoms reported by patients were fatigue, muscle pain, physically slowing down, poor sleep, and breathlessness, and patients said that their health related quality of life remained substantially worse one year after hospital discharge than before they had the SARS-CoV-2 infection.

A cluster analysis on the five month data revealed four distinct groups of patients based on the severity of symptoms they experienced: in 39% symptoms were considered mild, in 30% severe, in 20% very severe, and in 11% they were moderate or primarily affected cognition.

Blood samples taken at five months were analysed for around 300 substances linked to inflammation and immunity. These showed that patients in the “very severe” group had higher levels of substances associated with whole body inflammation, tissue damage, and tissue repair, while those reporting poor cognition appeared to have higher levels of substances linked to “brain fog,” suggesting possible neuro-inflammation.

Brightling said that the results suggested “an ongoing inflammatory process” and that other studies had indicated an increase in autoimmunity in some cases against specific organs such as heart or skeletal muscle. “We’re working very closely with immunologists to try to unpick that and see whether autoimmunity may be one of the key drivers [of long covid],” he said.

Source: Ingrid Torjesen. Covid-19: Long covid symptoms among hospital inpatients show little improvement after a year, data suggest. BMJ 2021;375:n3092. Published 15 December 2021. https://www.bmj.com/content/375/bmj.n3092 (Full text)

Establishing the prevalence of common tissue‐specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection

Summary:

Coronavirus 19 (COVID‐19) has been associated with both transient and persistent systemic symptoms that do not appear to be a direct consequence of viral infection. The generation of autoantibodies has been proposed as a mechanism to explain these symptoms. To understand the prevalence of autoantibodies associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, we investigated the frequency and specificity of clinically relevant autoantibodies in 84 individuals previously infected with SARS‐CoV‐2, suffering from COVID‐19 of varying severity in both the acute and convalescent setting. These were compared with results from 32 individuals who were on the intensive therapy unit (ITU) for non‐COVID reasons.

We demonstrate a higher frequency of autoantibodies in the COVID‐19 ITU group compared with non‐COVID‐19 ITU disease control patients and that autoantibodies were also found in the serum 3–5 months post‐COVID‐19 infection. Non‐COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID‐19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies.

Our results demonstrate that respiratory viral infection with SARS‐CoV‐2 is associated with the detection of a limited profile of tissue‐specific autoantibodies, detectable using routine clinical immunology assays. Further studies are required to determine whether these autoantibodies are specific to SARS‐CoV‐2 or a phenomenon arising from severe viral infections and to determine the clinical significance of these autoantibodies.

Source: Richter AG, Shields AM, Karim A, et al. Establishing the prevalence of common tissue-specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection. Clin Exp Immunol. 2021;205(2):99-105. doi:10.1111/cei.13623 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239842/ (Full article)

Diverse functional autoantibodies in patients with COVID-19

Abstract:

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7 to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome).

We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.

Source: Wang EY, Mao T, Klein J, Dai Y, Huck JD, Jaycox JR, Liu F, Zhou T, Israelow B, Wong P, Coppi A, Lucas C, Silva J, Oh JE, Song E, Perotti ES, Zheng NS, Fischer S, Campbell M, Fournier JB, Wyllie AL, Vogels CBF, Ott IM, Kalinich CC, Petrone ME, Watkins AE; Yale IMPACT Team, Dela Cruz C, Farhadian SF, Schulz WL, Ma S, Grubaugh ND, Ko AI, Iwasaki A, Ring AM. Diverse functional autoantibodies in patients with COVID-19. Nature. 2021 Jul;595(7866):283-288. doi: 10.1038/s41586-021-03631-y. Epub 2021 May 19. PMID: 34010947. https://pubmed.ncbi.nlm.nih.gov/34010947/

Breast implant illness: scientific evidence of its existence

Abstract:

Introduction: More than one million breast augmentation procedures using silicone breast implants (SBI) have been performed worldwide. Adverse events of SBI include local complications such as pain, swelling, redness, infections, capsular contracture, implant rupture and gel-bleed. Furthermore, patients experience systemic symptoms such as chronic fatigue, arthralgias, myalgias, pyrexia, sicca, and cognitive dysfunction. These symptoms received different names such as autoimmune/inflammatory syndrome induced by adjuvants (ASIA) due to silicone incompatibility syndrome and breast implant illness (BII). Because of chronic immune activation, BII/ASIA, allergies, autoimmune diseases, immune deficiencies and finally lymphomas may develop in SBI patients.

Areas covered: Causality for SBI-related BII/ASIA is reviewed. To address the role of silicone implants in promoting causality, we utilized the Bradford-Hill criteria, with results highlighted in this article.

Expert opinion: We conclude that there is a causal association between SBIs and BII/ASIA. Using data derived from patients with BII/ASIA and from other medically implanted devices, there appears to be clear pathogenic relationship between SBI and BII/ASIA. Breast implants cause characteristic systemic reactions in certain women, leading to symptoms of sufficient severity to warrant device removal. The morbidity suffered is variable. SBI removal resolves the symptoms in most women and removal is the most effective treatment.

Source: Cohen Tervaert JW, Mohazab N, Redmond D, van Eeden C, Osman M. Breast implant illness: scientific evidence of its existence. Expert Rev Clin Immunol. 2021 Dec 9. doi: 10.1080/1744666X.2022.2010546. Epub ahead of print. PMID: 34882509. https://pubmed.ncbi.nlm.nih.gov/34882509/

Post COVID-19 Syndrome in Patients with Asymptomatic/Mild Form

Abstract:

Post COVID-19 Syndrome (PCS) is a complex of various symptoms developing a month or more after the acute phase of the disease. The cases of PCS development among patients with asymptomatic/mild forms are frequently reported; however, the pathogenesis of PCS in this group of patients is still not completely clear. The publications about COVID-19 which were published in online databases from December 2019 to September 2021 are analyzed in this review. According to the analysis, PCS develops on average in 30-60% of patients, mainly among women. Fatigue, shortness of breath, cough, and anosmia were reported as the most common symptoms. The possible association between the described PCS symptoms and brain damage was revealed.

We assume the possibility of an alternative course of COVID-19, which develops in genetically predisposed individuals with a stronger immune response, in which it predominantly affects the cells of the nervous system, possibly with the presence of an autoimmune component, which might have similarity with chronic fatigue syndrome or autoimmune disautonomia. Thus, the gender (female) and the presence of anosmia during an asymptomatic or mild course of the disease can be predictive factors for the development of PCS, which can be caused by autoimmune damage to neurons, glia, and cerebral vessels.

Source: Malkova A, Kudryavtsev I, Starshinova A, Kudlay D, Zinchenko Y, Glushkova A, Yablonskiy P, Shoenfeld Y. Post COVID-19 Syndrome in Patients with Asymptomatic/Mild Form. Pathogens. 2021 Oct 30;10(11):1408. doi: 10.3390/pathogens10111408. PMID: 34832564. https://pubmed.ncbi.nlm.nih.gov/34832564/

The reification of the clinical diagnosis of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as an immune and oxidative stress disorder: construction of a data-driven nomothethic network and exposure of ME/CFS subgroups

Abstract:

The approach towards myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) remains in a permanent state of crisis with fierce competition between the psychosocial school, which attributes ME/CFS to the perception of effort, and the medical approach (Maes and Twisk, BMC Med, 2010,8,35). The aim of this paper is to review how to construct a nomothetic model of ME/CFS using Partial Least Squares (PLS) path analysis and ensembling causome (bacterial translocation as assessed with IgM/IgA responses to LPS), protectome (lowered coenzyme Q10), adverse outcome pathways (AOP) including increased lysozyme, CD38+ T cell activation, cell-mediated immune activation (CMI), and IgM responses to oxidative specific epitopes and NO-adducts (IgM OSENO).

Using PLS, we trained, tested and validated this knowledge- and data-driven causal ME/CFS model, which showed adequate convergence, construct and replicability validity. This bottom-up explicit data model of ME/CFS objectivates the descriptive narratives of the ME/CFS phenome, using causome-protectome-AOP data, whereby the abstract concept ME/CFS is translated into pathways, thereby securing the reification of the ME/CFS phenome.

We found that 31.6% of the variance in the physiosomatic symptom dimension of ME/CFS was explained by the cumulative effects of CMI and CD38+ activation, IgM OSENO, IgA LPS, lysozyme (all positive) and coenzyme Q10 (inversely). Cluster analysis performed on the PLS-generated latent vector scores of all feature sets exposed three distinct immune groups of ME/CFS, namely one with increased lysozyme, one with increased CMI + CD38 activation + depressive symptoms, and another with increased bacterial translocation + autoimmune responses to OSENO

Source: Maes M, Kubera M, Stoyanova K, Leunis JC. The reification of the clinical diagnosis of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as an immune and oxidative stress disorder: construction of a data-driven nomothethic network and exposure of ME/CFS subgroups. Curr Top Med Chem. 2021 Jul 27. doi: 10.2174/1568026621666210727170147. Epub ahead of print. PMID: 34315375. https://pubmed.ncbi.nlm.nih.gov/34315375/