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Multicenter Study
. 2023 Oct;71(5):717-724.
doi: 10.1007/s12026-023-09384-2. Epub 2023 May 12.

SARS-CoV-2 antibodies in inflammatory neurological conditions: a multicentre retrospective comparative study

Cecilia Zivelonghi #  1 , Alessandro Dinoto #  2 , Sarosh R Irani  3   4   5 , Andrew McKeon  6   7 , Andrea Pilotto  8 , Alessandro Padovani  8 , Stefano Masciocchi  8 , Eugenio Magni  9 , Chiara R Mancinelli  10 , Ruggero Capra  10 , Giorgia T Maniscalco  11   12 , Irene Volonghi  8 , Ava Easton  13   14 , Daniela Alberti  1 , Gianluigi Zanusso  1 , Salvatore Monaco  1 , Gian Luca Salvagno  15   16 , Giuseppe Lippi  15 , Sergio Ferrari  1 , Sara Mariotto  17
Affiliations
Multicenter Study

SARS-CoV-2 antibodies in inflammatory neurological conditions: a multicentre retrospective comparative study

Cecilia Zivelonghi et al. Immunol Res. 2023 Oct.

Abstract

It is well established that neurological and non-neurological autoimmune disorders can be triggered by viral infections. It remains unclear whether SARS-CoV-2 infection induces similar conditions and whether they show a distinctive phenotype. We retrospectively identified patients with acute inflammatory CNS conditions referred to our laboratory for antibody testing during the pandemic (March 1 to August 31, 2020). We screened SARS-COV-2 IgA/IgG in all sera by ELISA and confirmed the positivity with additional assays. Clinical and paraclinical data of SARS-COV-2-IgG seropositive patients were compared to those of seronegative cases matched for clinical phenotype, geographical zone, and timeframe. SARS-CoV-2-IgG positivity was detected in 16/339 (4%) sera, with paired CSF positivity in 3/16. 5 of these patients had atypical demyelinating disorders and 11 autoimmune encephalitis syndromes. 9/16 patients had a previous history of SARS-CoV-2 infection and 6 of them were symptomatic. In comparison with 32 consecutive seronegative controls, SARS-CoV-2-IgG-positive patients were older, frequently presented with encephalopathy, had lower rates of CSF pleocytosis and other neurological autoantibodies, and were less likely to receive immunotherapy. When SARS-CoV-2 seropositive versus seronegative cases with demyelinating disorders were compared no differences were seen. Whereas seropositive encephalitis patients less commonly showed increased CSF cells and protein, our data suggest that an antecedent symptomatic or asymptomatic SARS-CoV-2 infection can be detected in patients with autoimmune neurological conditions. These cases are rare, usually do not have specific neuroglial antibodies.

Keywords: Demyelinating disorders; Encephalitis; SARS-CoV-2; Viral trigger.

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Conflict of interest statement

S Irani is a coapplicant and receives royalties on a licensed patent application WO/210/046716 (U.K. patent no., PCT/GB2009/051441) entitled “Neurological Autoimmune Disorders” and has filed “Diagnostic Strategy to improve specificity of CASPR2 antibody detection (PCT/G82019 /051257); he has received honoraria and research support from UCB, Immunovant, MedImmun, Roche, Cerebral therapeutics, ADC therapeutics, CSL Behring and ONO Pharma; A.McKeon has received royalties pertaining to the commercialization of septin-5 and MAP1B antibodies for diagnosis of autoimmune neurological diseases, has patents pending for neural IgGs as biomarkers for diagnosis and treatment of autoimmune neurological disorders, and has received research support from Euroimmun AG; APi served in the advisory board of Z-cube (technology division of Zambon pharmaceuticals), he received honoraria from Z-cube s.r.l., Biomarin, Zambon, Abbvie, Nutricia and Chiesi pharmaceuticals. He received research support from Vitaflo Germany and Zambon Italy; APa is consultant and served on the scientific advisory board of GE Healthcare, Eli-Lilly and Actelion Ltd Pharmaceuticals, received speaker honoraria from Nutricia, PIAM, Lansgstone Technology, GE Healthcare, Lilly, UCB Pharma and Chiesi Pharmaceuticals, he is funded by Grant of Ministry of University (MURST); the other authors report no disclosures relevant to the manuscript. S Mariotto is associate editor of Immunologic Research.

Figures

Fig. 1
Fig. 1
Flowchart of the study design
Fig. 2
Fig. 2
Monthly data of samples referred for antibody testing (total, grey, and divided according to the clinical phenotype of demyelinating disorders, orange, and encephalitis, light blue) in relation to the number SARS-CoV-2 IgG-positive patients (yellow) per month
See this image and copyright information in PMC

References

    1. Ellul MA, Benjamin L, Singh B, Lant S, Michael BD, Easton A, et al. Neurological associations of COVID-19. Lancet Neurol [Internet] Elsevier Ltd. 2020;19:767–83. doi: 10.1016/S1474-4422(20)30221-0. - DOI - PMC - PubMed
    1. Pilotto A, Masciocchi S, Volonghi I, Crabbio M, Magni E, de Giuli V, et al. SARS-CoV-2 related encephalopaties (ENCOVID) Study Group, Clinical Presentation and Outcomes of Severe Acute Respiratory Syndrome Coronavirus 2–Related Encephalitis: The ENCOVID Multicenter Study, The Journal of Infectious Diseases, 2021;223:28–37. 10.1093/infdis/jiaa609 - PMC - PubMed
    1. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579:265–269. doi: 10.1038/s41586-020-2008-3. - DOI - PMC - PubMed
    1. Patone M, Handunnetthi L, Saatci D, Pan J, Katikireddi SV, Razvi S, et al. Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection. Nat Med Springer US. 2021;27:2144–53. doi: 10.1038/s41591-021-01556-7. - DOI - PMC - PubMed
    1. Alexopoulos H, Magira E, Bitzogli K, Kafasi N, Vlachoyiannopoulos P, Tzioufas A, et al. Anti-SARS-CoV-2 antibodies in the CSF, blood-brain barrier dysfunction, and neurological outcome: Studies in 8 stuporous and comatose patients. Neurol(R) Neuroimmunol Neuroinflamm. 2020;7:4–8. - PMC - PubMed

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