Adaptive Immunity and the Risk of Autoreactivity in COVID-19

Moody, Rhiane; Wilson, Kirsty; Flanagan, Katie L.; Jaworowski, Anthony; Plebanski, Magdalena

doi:10.3390/ijms22168965

Cited by 40 publications

(27 citation statements)

References 88 publications

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“…One mechanism through which SARS-CoV-2 infection is thought to lead to the development of autoimmunity is that of molecular mimicry. Molecular mimicry happens when the same lymphocyte receptor recognizes both a self-protein and a foreign antigen because of their structural similarity, which can lead to immune cross-reactivity [ 8 ]. Molecular mimicry is known to have an important role in the pathogenesis of systemic rheumatologic disorders like SLE, rheumatoid arthritis, Sjogren syndrome, and SSc [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Systemic Sclerosis (SSc) After COVID-19: A Case Report

Chandra¹,

Kahaleh²

2022

Cureus

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Since the start of the global pandemic caused by coronavirus disease 2019 (COVID-19), there have been numerous reports of autoimmune and rheumatological disorders developing after infection with SARS-CoV-2. To date, there has been only one reported case of systemic sclerosis (SSc) developing after SARS-CoV-2 infection. Here, we present another case of SSc developing after infection with SARS-CoV-2.A 48-year-old female with past medical history of anxiety and depression presented to the rheumatology clinic after being referred for further evaluation of abnormal labs, Raynaud's phenomenon, and other concerning symptoms. Shortly after hospitalization for COVID-19 pneumonia, she began experiencing symptoms that included fatigue, xerostomia, dysphagia, bilateral lower extremity weakness, dyspnea with exertion, unintentional weight loss, and diffuse skin hyperpigmentation. Labs ordered shortly before presentation were significant for antinuclear antibody (ANA) titer > 1:1280. Physical exam was remarkable for puffy fingers, sclerodactyly of the fingers, diffuse skin hyperpigmentation, and abnormal nailfold capillaries. Anti-RNA polymerase III, anti-Scl-70, anti-centromere, anti-SSA, anti-SSB, anti-Smith, and anti-Smith/RNP antibodies were all negative. BNP, aldolase, and serum myoglobin levels were within normal limits while creatine phosphokinase level was slightly decreased. Pulmonary function testing showed reduced diffusion capacity with normal lung mechanics and volumes. High-resolution CT scan of the chest showed interstitial lung disease, with findings suggestive of nonspecific interstitial pneumonia. Transthoracic echocardiogram showed mild elevation of right ventricular systolic pressure, but pulmonary hypertension was not found on right heart catheterization. Esophagogastroduodenoscopy (EGD) with biopsy performed for evaluation of esophageal dysphagia showed sliding hiatal hernia, irregular Z-line, and gastric hyperemia. Biopsy of the distal esophagus was consistent with Barrett's esophagus. The patient was diagnosed with SSc according to the 2013 American College of Rheumatology/European League Against Rheumatism (ACR-EULAR) classification criteria for SSc. She is currently being treated with mycophenolate mofetil, amlodipine, methotrexate, and prednisone.

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Section: Discussionmentioning

confidence: 99%

Systemic Sclerosis (SSc) After COVID-19: A Case Report

Chandra¹,

Kahaleh²

2022

Cureus

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“…The plausible explanations for the induction of a myasthenic crisis by the COVID-19 vaccine may be attributed to two possible mechanisms: molecular mimicry, and bystander activation. In the former, antigens produced from the mRNA vaccine are recognized by the body as being similar to host tissue antigens resulting in the formation of antibodies that are cross-reactive to both the COVID-19 virus as well as proteins present at the post-synaptic membrane such as AChRs, MuSK receptor, LDL receptor-4, or agrin [ 13 ]. In the bystander hypothesis, a previously existing self-antigen is released after activation of the immune system by the vaccine thus resulting in activation of T-cells.…”

Section: Discussionmentioning

confidence: 99%

“…This immune response leads to enhanced targeting and destruction of proteins at the NMJ, resulting in further deterioration of the condition. Given the present case, the bystander hypothesis is more applicable due to the existing diagnosis of MG; however, molecular mimicry may have also been involved in the exacerbation of the disease [ 13 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

An Interesting Case of Fatal Myasthenic Crisis Probably Induced by the COVID-19 Vaccine

Sonigra¹,

Sarna²,

Vaghela³

et al. 2022

Cureus

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A myasthenic crisis is a severe, life-threatening exacerbation of myasthenia gravis that causes a rapid onset of muscle weakness and fatigue that may result in tetraparesis, dyspnea, respiratory insufficiency, aspiration, and death. Bulbar muscle functions are markedly affected resulting in depressed cough reflex, swallowing, and speech. Thus, mechanical ventilation, supportive feeding, and critical care are essential for the survival of patients in a myasthenic crisis. Numerous precipitating factors of this condition are well known and include infections, various medications, pregnancy, and childbirth. Patients with myasthenia gravis are at a considerably higher risk of developing a debilitating coronavirus disease 2019 (COVID-19) infection due to the associated immunosuppression resulting from long-term corticosteroid use, which makes vaccination of such individuals necessary. However, the relationship between an exacerbation of myasthenia gravis and the COVID-19 vaccination is currently unknown. In this paper, we report the case of a 55-year-old male patient who developed a myasthenic crisis after receiving the first dose of the ChAdOx1-S (recombinant) vaccine (AstraZeneca batch number 210157; AstraZeneca plc, Cambridge, United Kingdom). Despite the administration of aggressive and intensive treatment over a period of 29-day hospitalization, the myasthenic crisis could not be reversed and the patient ultimately deteriorated and succumbed from multiple myocardial infarction events and organ failures. While it is still uncommon, evidence associating the effects of the vaccine to the development of a crisis is mounting; therefore, it is crucial for clinicians to promptly identify clinical features that suggest an exacerbation of myasthenia gravis in order to intervene at the earliest possible stage for a more favorable outcome. The myasthenia gravis patient should be informed about the possible association between COVID-19 vaccination and the development of a myasthenic crisis.

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“…Relating to SARS, the autoantibodies’ target, LINE1 ORF2p, was prominently stained post-mortem in lung macrophages (residing in blood vessels), leading the authors to suspect a build-up of autoreactive CD4+ Th cells and, thus, an autoimmune loop in SARS [ 55 ]. Importantly, there is also increasing evidence for an autoimmune pathogenesis in severe COVID-19 [ 13 – 27 , 66 , 67 ]. One explanation for autoantibody formation is by molecular mimicry, i.e.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 and human retroelements: a case for molecular mimicry?

Koch

2022

BMC Genom Data

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Background The factors driving the late phase of COVID-19 are still poorly understood. However, autoimmunity is an evolving theme in COVID-19’s pathogenesis. Additionally, deregulation of human retroelements (RE) is found in many viral infections, and has also been reported in COVID-19. Results Unexpectedly, coronaviruses (CoV) – including SARS-CoV-2 – harbour many RE-identical sequences (up to 35 base pairs), and some of these sequences are part of SARS-CoV-2 epitopes associated to COVID-19 severity. Furthermore, RE are expressed in healthy controls and human cells and become deregulated after SARS-CoV-2 infection, showing mainly changes in long interspersed nuclear element (LINE1) expression, but also in endogenous retroviruses. Conclusion CoV and human RE share coding sequences, which are targeted by antibodies in COVID-19 and thus could induce an autoimmune loop by molecular mimicry.

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Adaptive Immunity and the Risk of Autoreactivity in COVID-19

Cited by 40 publications

References 88 publications

Systemic Sclerosis (SSc) After COVID-19: A Case Report

Systemic Sclerosis (SSc) After COVID-19: A Case Report

An Interesting Case of Fatal Myasthenic Crisis Probably Induced by the COVID-19 Vaccine

SARS-CoV-2 and human retroelements: a case for molecular mimicry?

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