Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms

Wallukat, Gerd; Hohberger, Bettina; Wenzel, Katrin; Fürst, Julia; Schulze-Rothe, Sarah; Wallukat, Anne; Hönicke, Anne Sophie; Müller, Johannes

doi:10.1016/j.jtauto.2021.100100

Cited by 273 publications

(251 citation statements)

References 52 publications

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“…For acute SARS-CoV-2 infection, the development of ANA IgA autoantibodies has been shown [ 14 ] and the presence of high-titer serum IgG antibodies targeting the GD1b ganglioside has been demonstrated in certain neurologically affected patients [ 13 ]. In a cohort of 31 patients with long COVID, functionally active autoantibodies targeting G-protein–coupled receptors were detected in a high proportion of patients experiencing a variety of post–COVID-19 symptoms [ 15 ]. Although the nature of the self-antigens recognized by autoimmune-like antibodies is diverse, a general characteristic shared by infections is the generation of ANAs, which appear during acute infection and may remain at lower levels during chronic infections [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Persistent Symptoms in Adult Patients 1 Year After Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study

Seeßle

Waterboer

Hippchen

et al. 2021

Clinical Infectious Diseases

420

309

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Background Long COVID is defined as the persistence of symptoms beyond 3 months after SARS-CoV-2 infection. To better understand the long-term course and etiology of symptoms we analyzed a cohort of COVID-19 patients prospectively. Methods Patients were included at 5 months after acute COVID-19 in this prospective, non-interventional follow-up study. Patients followed until 12 months after COVID-19 symptom onset (n=96, 32.3% hospitalised, 55.2% females) were included in this analysis of symptoms, quality of life (based on a SF-12 survey), laboratory parameters including antinuclear antibodies (ANA), and SARS-CoV-2 antibody levels. Results At month 12, only 22.9% of patients were completely free of symptoms and the most frequent symptoms were reduced exercise capacity (56.3%), fatigue (53.1%), dyspnoea (37.5%), concentration problems (39.6%), problems finding words (32.3%), and sleeping problems (26.0%). Females showed significantly more neurocognitive symptoms than males. ANA titres were ≥1:160 in 43.6% of patients at 12 months post COVID-19 symptom onset, and neurocognitive symptom frequency was significantly higher in the group with an ANA titre ≥1:160 compared to <1:160. Compared to patients without symptoms, patients with at least one long COVID symptom at 12 months did not differ significantly with respect to their SARS-CoV-2-antibody levels, but had a significantly reduced physical and mental life quality compared to patients without symptoms. Conclusions Neurocognitive long COVID symptoms can persist at least for one year after COVID-19 symptom onset, and reduce life quality significantly. Several neurocognitive symptoms were associated with ANA titre elevations. This may indicate autoimmunity as cofactor in aetiology of long COVID.

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Section: Discussionmentioning

confidence: 99%

Persistent Symptoms in Adult Patients 1 Year After Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study

Seeßle

Waterboer

Hippchen

et al. 2021

Clinical Infectious Diseases

420

309

View full text Add to dashboard Cite

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“…These are also illnesses of uncertain aetiology, sometimes triggered by a viral infection, yet they do have traits that differentiate them from LC (12) . This article (17) explains that a combination of antibodies and ischemic cofactors or inflammations can work to maintain an inflammation process, which explains the persistence of symptoms in LC patients, indicating and indeed demonstrating that certain antibodies can affect the maturing and degranulation of cardiac mast cells, contributing to said inflammation.…”

Section: Humoral Response In Lc Patientsmentioning

confidence: 83%

Analysis of cell-mediated immunity in people with long COVID

Montes¹,

Domènech²,

Guerrero³

et al. 2021

Preprint

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Introduction: The objective of this study is to analyse the specific immune response against SARS-CoV-2 in those affected by Long Covid (LC), attributable to T cells (cell-mediated immunity) and to carry out a parallel analysis of the humoral response and lymphocyte typing. Methodology: Descriptive cross-sectional study of 74 patients with LC for at least 4 months since diagnosis. The collected data were: information on the COVID-19 episode and the persistent symptoms, medical history and a specific cell-mediated immunity to SARS-CoV-2 through flow cytometry, assessing the release of interferon-gamma (IFN-Ɣ) by T4 lymphocytes, T8 lymphocytes and NK cells. Descriptive and comparative analyses were carried out. Results: Patients with LC had negative serology for Covid-19 in 89% of cases but 96% showed specific cellular immunity to SARS-CoV-2 an average of 9.5 months after infection: 89% of this response corresponded to T8 lymphocytes, 58% to NK cells, and 51% to T4 lymphocyte (20% negligibly positive). Most of them had altered immune cell typing and we found that T4 lymphocyte counts were low in 34% of cases and NK cell high in 64%. Macrophage populations were detected in the peripheral blood of 7% of them. Patients displayed a higher percentage of illnesses related to ″abnormal″ immune responses, either preceding SARS-CoV-2 infection (43%) or following it in 23% of cases. Conclusion: The immune system appears to have an important involvement in the development of LC and viral persistence could be the cause or consequence of it. Further analysis with a control group should be performed.

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“…For sure it will interact with functionally active autoantibodies against G-protein-coupled receptors. Functionally active autoantibodies against G-protein-coupled receptors have already been found in many Long-COVID patients suffering from a variety of different neurological and/or cardiological diseases [ 14 ].…”

Section: Resultsmentioning

confidence: 99%

“…These different types of anti-SARS-CoV-2 ABs have to be distinguished. Even the occurrence of functionally active autoantibodies against G-protein-coupled receptors in patients suffering from Long-COVID symptoms has already been reported [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Aptamer BC 007’s Affinity to Specific and Less-Specific Anti-SARS-CoV-2 Neutralizing Antibodies

Haberland

Krylova

Nikolenko

et al. 2021

Viruses

Self Cite

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COVID-19 is a pandemic respiratory disease that is caused by the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anti-SARS-CoV-2 antibodies are essential weapons that a patient with COVID-19 has to combat the disease. When now repurposing a drug, namely an aptamer that interacts with SARS-CoV-2 proteins for COVID-19 treatment (BC 007), which is, however, a neutralizer of pathogenic autoantibodies in its original indication, the possibility of also binding and neutralizing anti-SARS-CoV-2 antibodies must be considered. Here, the highly specific virus-neutralizing antibodies have to be distinguished from the ones that also show cross-reactivity to tissues. The last-mentioned could be the origin of the widely reported SARS-CoV-2-induced autoimmunity, which should also become a target of therapy. We, therefore, used enzyme-linked immunosorbent assay (ELISA) technology to assess the binding of well-characterized publicly accessible anti-SARS-CoV-2 antibodies (CV07-209 and CV07-270) with BC 007. Nuclear magnetic resonance spectroscopy, isothermal calorimetric titration, and circular dichroism spectroscopy were additionally used to test the binding of BC 007 to DNA-binding sequence segments of these antibodies. BC 007 did not bind to the highly specific neutralizing anti-SARS-CoV-2 antibody but did bind to the less specific one. This, however, was a lot less compared to an autoantibody of its original indication (14.2%, range 11.0–21.5%). It was also interesting to see that the less-specific anti-SARS-CoV-2 antibody also showed a high background signal in the ELISA (binding on NeutrAvidin-coated or activated but noncoated plastic plate). These initial experiments suggest that the risk of binding and neutralizing highly specific anti-SARS CoV-2 antibodies by BC 007 should be low.

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Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms

Cited by 273 publications

References 52 publications

Persistent Symptoms in Adult Patients 1 Year After Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study

Persistent Symptoms in Adult Patients 1 Year After Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study

Analysis of cell-mediated immunity in people with long COVID

Aptamer BC 007’s Affinity to Specific and Less-Specific Anti-SARS-CoV-2 Neutralizing Antibodies

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