key: cord-258092-a4e59c7z
authors: Pfeuffer, Steffen; Pawlowski, Matthias; Joos, Gunther S.; Minnerup, Jens; Meuth, Sven G.; Dziewas, Rainer; Wiendl, Heinz
title: Autoimmunity complicating SARS-CoV-2 infection in selective IgA-deficiency
date: 2020-08-12
journal: Neurol Neuroimmunol Neuroinflamm
DOI: 10.1212/nxi.0000000000000881
sha: 
doc_id: 258092
cord_uid: a4e59c7z

nan

However, because of rapidly developing respiratory insufficiency, intubation became necessary on day 10. Chest x-ray and CT scan showed signs suggestive of COVID-19.

During ICU treatment, the patient recovered from COVID-19, and nasopharyngeal swabs for SARS-CoV-2 were repeatedly negative (first on day 15). The patient was weaned from ventilatory support, and extubation was performed on day 17. Blood glucose levels remained well controlled throughout after IV insulin substitution.

However, restrictive lung disorder resulting from diaphragmatic paralysis rapidly evolved, and poor management of pharyngeal secretions forced reintubation within 24 hours. A rapidly progressive proximal tetraparesis and dysautonomia with tachycardia and absent heart rate variability were first noticed on day 19 and repeatedly let to self-limiting, symptomatic bradycardia on day 20.

MRI scans of the brain and cervical cord were unremarkable. CSF analysis showed albuminocytologic dissociation (CSF total protein: 1421 mg/L, CSF cell count: 2/μL, and CSF oligoclonal bands were negative). SARS-CoV-2 was not detectable in the CSF. Nerve conduction studies revealed widespread axonal damage as indicated by reduced compound motor action This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

For the latest articles, invited commentaries, and blogs from physicians around the world NPub.org/COVID19 potentials (figure, B). Antibodies against Gd1B were positive, whereas antibodies against other gangliosides were negative.

Laboratory analysis revealed selective immunoglobulin A deficiency (sIgAD; serum IgA <0.05g/L) but was otherwise unremarkable for autoimmune or hematologic disorders. Virologic and serologic testing was negative for hepatitis, HIV, herpes viruses, other respiratory viruses, and Campylobacter.

We performed 5 courses of plasma exchange. After this, we observed early recovery with increasing muscle strength and reemerging muscle reflexes. However, bulbar palsy persisted and prompted early tracheostomy on day 22. Decannulation was performed on day 45. Currently, symptoms mostly resolved but mild neurogenic dysphagia persists. C-peptide levels remain below thresholds, and insulin treatment is continued.

We believe that our patient suffered from sIgAD since childhood but remained undiagnosed in the absence of symptoms until autoimmunity was finally induced by COVID-19. SARS-CoV-2 has been identified as a potential trigger for GBS because its spike viral protein interacts with ganglioside antigens on human cells and thereby paves the way for an antiganglioside immune reaction. 1 Such association has not been shown yet for T1D, but previous reports on the development of DKA within already 1 week after nivolumab treatment 2 indicate that a single trigger can result in rapid-onset T1D in susceptible patients and normal HbA1c levels render preexisting yet undiscovered T1D unlikely here. In addition, sIgAD is a known risk factor for T1D. 3 Moreover, previous cases on GBS after COVID-19 mostly showed an onset within 5-10 days supporting that COVID-19 is a sufficient trigger of rapid-onset autoimmunity. 1 However in GBS, the role of sIgAD is less clear, although asymptomatic ganglioside antibodies are more common in patients with sIgAD compared with the general population. 4 Clinically, our case here shares many features with previously published reports. Our patients suffered from a predominantly axonal variant of GBS, which has been observed before. Previous patients also developed GBS already within 7-10 days after the onset of COVID-19. 1 Furthermore, bulbar involvement has been described in previous cases. 5, 6 Especially, it was present in a case of Miller-Fisher syndrome that also presented with Gd1b antibodies. 5 We have not observed ophthalmoplegia, yet dysphagia subsequent to bulbar palsy resulted in necessity for tracheostomy in our patient as described before. 7 Finally, our findings expand the spectrum of autoimmunity after COVID-19. Although COVID-19 was repeatedly demonstrated as an inducer of GBS alone, we believe that the preexisting sIgAD significantly contributed to the development of 2 different autoimmune disorders after COVID-19. 

Guillain-Barre syndrome: the first documented COVID-19-triggered autoimmune neurologic disease: more to come with myositis in the offing

Rapid-onset diabetic ketoacidosis secondary to nivolumab therapy

Selective IgA deficiency in autoimmune diseases

Multireactive pattern of serum autoantibodies in asymptomatic individuals with immunoglobulin A deficiency

Cranial neuropathies and COVID-19: neurotropism and autoimmunity

Miller Fisher Syndrome and polyneuritis cranialis in COVID-19

Intubation, tracheostomy, and decannulation in patients with Guillain-Barre-syndrome-does dysphagia matter?

Aventis. He has received compensation as a consultant from Biogen Idec, Merck Serono, Novartis, Roche, and Sanofi Genzyme. Heinz Wiendl also received research support from Bayer Healthcare, Bayer Vital, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, Sanofi US, and Teva. Go to Neurology.org/NN for full disclosures.