{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T08:00:14Z","timestamp":1771660814157,"version":"3.50.1"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,8,7]],"date-time":"2021-08-07T00:00:00Z","timestamp":1628294400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,7]],"date-time":"2021-08-07T00:00:00Z","timestamp":1628294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006747","name":"Fondazione Cassa di Risparmio di Verona Vicenza Belluno e Ancona","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006747","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Brain Research Foundation Verona, Italy","award":["2020"],"award-info":[{"award-number":["2020"]}]},{"DOI":"10.13039\/501100007052","name":"Universit\u00e0 degli Studi di Verona","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007052","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Immunol Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The persistence of neurological symptoms after SARS-CoV-2 infection, as well as the presence of late axonal damage, is still unknown. We performed extensive systemic and neurological follow-up evaluations in 107 out of 193 consecutive patients admitted to the COVID-19 medical unit, University Hospital of Verona, Italy between March and June 2020. We analysed serum neurofilament light chain (NfL) levels in all cases including a subgroup (<jats:italic>n<\/jats:italic>\u2009=\u200929) of patients with available onset samples. Comparisons between clinical and biomarker data were then performed. Neurological symptoms were still present in a significant number (<jats:italic>n<\/jats:italic>\u2009=\u200949) of patients over the follow-up. The most common reported symptoms were hyposmia (<jats:italic>n<\/jats:italic>\u2009=\u200911), fatigue (<jats:italic>n<\/jats:italic>\u2009=\u200928), myalgia (<jats:italic>n<\/jats:italic>\u2009=\u200914), and impaired memory (<jats:italic>n<\/jats:italic>\u2009=\u200911) and were more common in cases with severe acute COVID-19. Follow-up serum NfL values (15.2\u00a0pg\/mL, range 2.4\u201362.4) were within normal range in all except 5 patients and did not differentiate patients with vs without persistent neurological symptoms. In patients with available onset and follow-up samples, a significant (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) decrease of NfL levels was observed and was more evident in patients with a severe acute disease. Despite the common persistence of neurological symptoms, COVID-19 survivors do not show active axonal damage, which seems a peculiar feature of acute SARS-CoV-2 infection.<\/jats:p>","DOI":"10.1007\/s12026-021-09220-5","type":"journal-article","created":{"date-parts":[[2021,8,7]],"date-time":"2021-08-07T10:03:02Z","timestamp":1628330582000},"page":"553-557","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Neurological symptoms and axonal damage in COVID-19 survivors: are there sequelae?"],"prefix":"10.1007","volume":"69","author":[{"given":"Silvia","family":"Bozzetti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Zanzoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Alberti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Braggio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Carta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Piraino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Gabbiani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Girelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Nocini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Monaco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernesto","family":"Crisafulli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7806-3103","authenticated-orcid":false,"given":"Sara","family":"Mariotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,7]]},"reference":[{"key":"9220_CR1","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/S1474-4422(20)30221-0","volume":"19","author":"MA Ellul","year":"2020","unstructured":"Ellul MA, Benjamin L, Singh B, et al. Neurological associations of COVID-19. Lancet Neurol. 2020;19:767\u201383. https:\/\/doi.org\/10.1016\/S1474-4422(20)30221-0.","journal-title":"Lancet Neurol"},{"key":"9220_CR2","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1136\/jnnp-2020-323929","volume":"92","author":"A Pilotto","year":"2020","unstructured":"Pilotto A, Benussi A, Libri I, et al. COVID-19 impact on consecutive neurological patients admitted to the emergency department. J Neurol Neurosurg Psychiatry. 2020;92:218\u201320. https:\/\/doi.org\/10.1136\/jnnp-2020-323929.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"9220_CR3","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","volume":"14","author":"M Khalil","year":"2018","unstructured":"Khalil M, Teunissen CE, Otto M, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018;14:577\u201389. https:\/\/doi.org\/10.1038\/s41582-018-0058-z.","journal-title":"Nat Rev Neurol"},{"key":"9220_CR4","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1136\/jnnp-2020-323881","volume":"91","author":"S Mariotto","year":"2020","unstructured":"Mariotto S, Savoldi A, Donadello K, et al. Nervous system: subclinical target of SARS-CoV-2 infection. J Neurol Neurosurg Psychiatry. 2020;91:1010\u20132. https:\/\/doi.org\/10.1136\/jnnp-2020-323881.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"9220_CR5","doi-asserted-by":"publisher","first-page":"e1754","DOI":"10.1212\/WNL.0000000000010111","volume":"95","author":"N Kanberg","year":"2020","unstructured":"Kanberg N, Ashton NJ, Andersson LM, et al. Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19. Neurology. 2020;95:e1754\u20139. https:\/\/doi.org\/10.1212\/WNL.0000000000010111.","journal-title":"Neurology"},{"key":"9220_CR6","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1002\/ana.26004","volume":"89","author":"R Sutter","year":"2021","unstructured":"Sutter R, Hert L, De Marchis GM, et al. Serum neurofilament light chain levels in the intensive care unit: comparison between severely ill patients with and without COVID-19. Ann Neurol. 2021;89:610\u20136. https:\/\/doi.org\/10.1002\/ana.26004.","journal-title":"Ann Neurol"},{"key":"9220_CR7","doi-asserted-by":"publisher","unstructured":"Virhammar J, N\u00e4\u00e4s A, F\u00e4llmar D, et al. Biomarkers for CNS injury in CSF are elevated in COVID-19 and associated with neurological symptoms and disease severity. Eur J Neurol. 2020. https:\/\/doi.org\/10.1111\/ene.14703.","DOI":"10.1111\/ene.14703"},{"key":"9220_CR8","doi-asserted-by":"publisher","first-page":"3476","DOI":"10.1007\/s00415-020-10050-y","volume":"267","author":"M Ameres","year":"2020","unstructured":"Ameres M, Brandstetter S, Toncheva AA, Kabesch M, Leppert D, Kuhle J, Wellmann S. Association of neuronal injury blood marker neurofilament light chain with mild-to-moderate COVID-19. J Neurol. 2020;267:3476\u20138. https:\/\/doi.org\/10.1007\/s00415-020-10050-y.","journal-title":"J Neurol"},{"key":"9220_CR9","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1007\/s00415-019-09306-z","volume":"266","author":"S Mariotto","year":"2019","unstructured":"Mariotto S, Gajofatto A, Zuliani L, et al. Serum and CSF neurofilament light chain levels in antibody-mediated encephalitis. J Neurol. 2019;266:1643\u20138. https:\/\/doi.org\/10.1007\/s00415-019-09306-z.","journal-title":"J Neurol"},{"key":"9220_CR10","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1080\/00365513.2020.1730434","volume":"80","author":"CVB Hviid","year":"2020","unstructured":"Hviid CVB, Knudsen CS, Parkner T. Reference interval and preanalytical properties of serum neurofilament light chain in Scandinavian adults. Scand J Clin Lab Invest. 2020;80:291\u20135. https:\/\/doi.org\/10.1080\/00365513.2020.1730434.","journal-title":"Scand J Clin Lab Invest"},{"key":"9220_CR11","doi-asserted-by":"publisher","first-page":"e1338","DOI":"10.1212\/WNL.0000000000006282","volume":"91","author":"S Tiedt","year":"2018","unstructured":"Tiedt S, Duering M, Barro C, et al. Serum neurofilament light: a biomarker of neuroaxonal injury after ischemic stroke. Neurology. 2018;91:e1338\u201347. https:\/\/doi.org\/10.1212\/WNL.0000000000006282.","journal-title":"Neurology"},{"key":"9220_CR12","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.neulet.2018.12.042","volume":"698","author":"F Pujol-Calder\u00f3n","year":"2019","unstructured":"Pujol-Calder\u00f3n F, Portelius E, Zetterberg H, et al. Neurofilament changes in serum and cerebrospinal fluid after acute ischemic stroke. Neurosci Lett. 2019;698:58\u201363. https:\/\/doi.org\/10.1016\/j.neulet.2018.12.042.","journal-title":"Neurosci Lett"},{"key":"9220_CR13","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1097\/QAD.0000000000001950","volume":"32","author":"G Ulfhammer","year":"2018","unstructured":"Ulfhammer G, Ed\u00e9n A, Mellgren \u00c5, et al. Persistent central nervous system immune activation following more than 10 years of effective HIV antiretroviral treatment. AIDS. 2018;32:2171\u20138. https:\/\/doi.org\/10.1097\/QAD.0000000000001950.","journal-title":"AIDS"}],"container-title":["Immunologic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-021-09220-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12026-021-09220-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-021-09220-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T06:22:55Z","timestamp":1636525375000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12026-021-09220-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,7]]},"references-count":13,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["9220"],"URL":"https:\/\/doi.org\/10.1007\/s12026-021-09220-5","relation":{},"ISSN":["0257-277X","1559-0755"],"issn-type":[{"value":"0257-277X","type":"print"},{"value":"1559-0755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,7]]},"assertion":[{"value":"9 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Ethics Committee of Verona University Hospital (prog. 2785CESC Verona-Rovigo).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from each included patient.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate\/publication"}},{"value":"S. Ferrari received support for attending scientific meetings by Shire, Sanofi Genzyme, and Euroimmun. F. Piraino is an employee of the Quanterix Corporation. S. Mariotto received support for attending scientific meetings by Merck and Euroimmun and received speaker honoraria from Biogen. The other authors report no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}