Similarities between COVID-19 and anti-MDA5 syndrome: what can we learn for better care?

Giannini, Margherita; Ohana, Mickaël; Nespola, Benoît; Zanframundo, Giovanni; Gény, Bernard; Meyer, Alain

doi:10.1183/13993003.01618-2020

Cited by 57 publications

(46 citation statements)

References 13 publications

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“…COVID-19-associated thromboses, severe lung pathology, and hyperinflammation contribute to poor outcomes. These manifestations bear some similarities to those observed in rheumatic diseases, such as antiphospholipid syndrome, 3 rheumatic-associated lung disease, 4 and macrophage activation syndrome 5 secondary to SLE, for which B-cell depletion with rituximab has been shown to be effective. Antiphospholipid antibodies have also been reported in COVID-19 patients with thromboses, although it is unclear whether these antibodies are pathogenic in this context, 3 and lung CT features in some patients with COVID-19 resemble those of fibrotic organising pneumonia (eg, similar to anti-MDA5 anti-synthetase syndrome).…”

mentioning

confidence: 56%

“…Antiphospholipid antibodies have also been reported in COVID-19 patients with thromboses, although it is unclear whether these antibodies are pathogenic in this context, 3 and lung CT features in some patients with COVID-19 resemble those of fibrotic organising pneumonia (eg, similar to anti-MDA5 anti-synthetase syndrome). 4 It is plausible that anti-SARS-Cov-2 antibodies or immune complexes might potentially evoke monocyte or alveolar macrophage activation, thereby contributing to sustained secretion of proinflammatory cytokines and the development of pulmonary disease. Therefore, could adaptive immunity contribute to poor outcomes in COVID-19, signalling a role for rituximab?…”

mentioning

confidence: 99%

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B-cell depletion with rituximab in the COVID-19 pandemic: where do we stand?

Mehta

Porter

Chambers

et al. 2020

The Lancet Rheumatology

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mentioning

confidence: 56%

mentioning

confidence: 99%

B-cell depletion with rituximab in the COVID-19 pandemic: where do we stand?

Mehta

Porter

Chambers

et al. 2020

The Lancet Rheumatology

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“…A striking similarity in increasingly being recognized between severe COVID-19 and anti-MDA5 DM with a similar involvement of the lung, skin rashes, fever, fatigue and myalgia. Notably, similar blood cytokine profiles with elevated ferritin and C-reactive protein (CRP) supports the idea that severe COVID-19 may resemble a human model of anti-MDA DM [24][25][26]. The hyperinflammatory response triggered by COVID-19 in susceptible individuals culminates in widespread endothelial dysfunction, vasculopathy and thrombotic manifestations with a pathophysiologic overlap with anti-MDA5 DM [27].…”

Section: Infectionsmentioning

confidence: 81%

Understanding and managing anti-MDA 5 dermatomyositis, including potential COVID-19 mimicry

2021

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Anti-Melanoma Differentiation-Associated gene 5 (MDA-5) Dermatomyositis (MDA5, DM) is a recently identified subtype of myositis characteristically associated with Rapidly Progressive Interstitial Lung Disease (RP-ILD) and unique cutaneous features. We reviewed PubMed, SCOPUS and Web of Science databases and selected 87 relevant articles after screening 1485 search results, aiming to gain a better understanding of the pathophysiology, clinical features, diagnosis, and treatment approaches of anti-MDA-5 DM described in the literature. The etiopathogenesis is speculatively linked to an unidentified viral trigger on the background of genetic predisposition culminating in an acquired type I interferonopathy. The clinical phenotype is highly varied in different ethnicities, with new clinical features having been recently described, expanding the spectrum of cases that should raise the suspicion of anti-MDA-5 DM. Unfortunately, the diagnosis is frequently missed despite excessive mortality, calling for wider awareness of suspect symptoms. RP ILD is the major determinant of survival, treatment being largely based on observational studies with recent insights into aggressive combined immunosuppression at the outset.

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“…The melanoma differentiation-associated protein 5 (MDA5) is a receptor capable of detecting different type of RNA molecules [ 68 ]. Anti-MDA5 autoantibodies are associated with a rare disease of amyopathic dermatomyositis [ 69 ]. De Lorenzis et al found anti-MDA5 antibody in SARS-CoV-2-infected patients [ 70 ].…”

Section: Sars-cov-2 and Immune And Autoimmune Reactionsmentioning

confidence: 99%

Effects of Cell Proteostasis Network on the Survival of SARS-CoV-2

et al. 2021

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The proteostasis network includes all the factors that control the function of proteins in their native state and minimize their non-functional or harmful reactions. The molecular chaperones, the important mediator in the proteostasis network can be considered as any protein that contributes to proper folding and assembly of other macromolecules, through maturating of unfolded or partially folded macromolecules, refolding of stress-denatured proteins, and modifying oligomeric assembly, otherwise it leads to their proteolytic degradation. Viruses that use the hosts’ gene expression tools and protein synthesis apparatus to survive and replicate, are obviously protected by such a host chaperone system. This means that many viruses use members of the hosts’ chaperoning system to infect the target cells, replicate, and spread. During viral infection, increase in endoplasmic reticulum (ER) stress due to high expression of viral proteins enhances the level of heat shock proteins (HSPs) and induces cell apoptosis or necrosis. Indeed, evidence suggests that ER stress and the induction of unfolded protein response (UPR) may be a major aspect of the corona-host virus interaction. In addition, several clinical reports have confirmed the autoimmune phenomena in COVID-19-patients, and a strong association between this autoimmunity and severe SARS-CoV-2 infection. Part of such autoimmunity is due to shared epitopes among the virus and host. This article reviews the proteostasis network and its relationship to the immune system in SARS-CoV-2 infection.

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Similarities between COVID-19 and anti-MDA5 syndrome: what can we learn for better care?

Abstract: Since the end of 2019, the coronavirus disease 2019 (COVID-19) pandemic has struck worldwide, leading to more than 7 million cases by June 2020, with an approximately 5.5% mortality rate, mainly due to acute respiratory distress syndrome (ARDS) [1].

Cited by 57 publications

References 13 publications

B-cell depletion with rituximab in the COVID-19 pandemic: where do we stand?

B-cell depletion with rituximab in the COVID-19 pandemic: where do we stand?

Understanding and managing anti-MDA 5 dermatomyositis, including potential COVID-19 mimicry

Effects of Cell Proteostasis Network on the Survival of SARS-CoV-2

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