Neuro-axonal injury in COVID-19: the role of systemic inflammation and SARS-CoV-2 specific immune response.

Background

In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune response with regard to neuronal injury has not yet been investigated.

Methods

In a prospective cohort study, we recruited patients with mild-moderate (

Results

sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild-moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild-moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies.

Conclusion

Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels.

Informations de copyright

© The Author(s), 2022.

Déclaration de conflit d'intérêts

Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.C.S. and T.S. report grants from Orion Pharma, Abbott Nutrition International, B. Braun Medical, CSEM, Edwards Lifesciences Services, Kenta Biotech, Maquet Critical Care, Omnicare Clinical Research, Nestle, Pierre Fabre Pharma, Pfizer, Bard Medica, Abbott, Anandic Medical Systems, Pan Gas Healthcare, Bracco, Hamilton Medical, Fresenius Kabi, Getinge Group Maquet, Dräger, Teleflex Medical, GlaxoSmithKline, Merck Sharp and Dohme, Eli Lilly and Company, Baxter, Astellas, Astra Zeneca, CSL Behring, Novartis, Covidien, Hemotune, Phagenesis, and Nycomed, outside the submitted work. D.L. is CMO of GeNeuro; he has received personal compensation for consulting and speaking, and travel reimbursement from Quanterix, Roche, Novartis, Orion, GeNeuro, and Sanofi, outside the submitted work. J.K. reports grants from Biogen, Novartis, Roche, Swiss MS Society, Sanofi, University of Basel, Swiss National Research Foundation, Merck, and Celgene, outside the submitted work. D.L. is CMO of GeNeuro; he has received personal compensation for consulting and speaking, and travel reimbursement from Quanterix, Roche, Novartis, Orion, GeNeuro, and Sanofi, outside the submitted work. S.L.L. reports grants from Swiss National Science Foundation, European Union’s Horizon 2020 research and innovation program, and HEARit Eureka Eurostars/European Commission, outside the submitted work.