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Cells
Volume 10
Issue 2
10.3390/cells10020386
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Article

Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations

by
Bing Sun
1,
Norina Tang
1,
Michael J. Peluso
2,
Nikita S. Iyer
3,
Leonel Torres
3,
Joanna L. Donatelli
3,
Sadie E. Munter
3,
Christopher C. Nixon
3,
Rachel L. Rutishauser
2,
Isabel Rodriguez-Barraquer
2,
Bryan Greenhouse
2,
John D. Kelly
4,
Jeffrey N. Martin
4,
Steven G. Deeks
2,
Timothy J. Henrich
3 and
Lynn Pulliam
1,5,*
1
Department of Laboratory Medicine, San Francisco VA Health Care System, San Francisco, CA 94121, USA
2
Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
3
Division of Experimental Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
4
Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA 94158, USA
5
Department of Laboratory Medicine and Medicine, University of California at San Francisco, San Francisco, CA 94143, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Ritva Tikkanen
Cells 2021, 10(2), 386; https://doi.org/10.3390/cells10020386
Received: 12 January 2021 / Revised: 9 February 2021 / Accepted: 10 February 2021 / Published: 13 February 2021
(This article belongs to the Collection Novel Biomarkers for Alzheimer’s Disease and Other Neurodegenerative Diseases)
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Abstract

As the SARS-CoV-2 pandemic continues, reports have demonstrated neurologic sequelae following COVID-19 recovery. Mechanisms to explain long-term neurological sequelae are unknown and need to be identified. Plasma from 24 individuals recovering from COVID-19 at 1 to 3 months after initial infection were collected for cytokine and antibody levels and neuronal-enriched extracellular vesicle (nEV) protein cargo analyses. Plasma cytokine IL-4 was increased in all COVID-19 participants. Volunteers with self-reported neurological problems (nCoV, n = 8) had a positive correlation of IL6 with age or severity of the sequalae, at least one co-morbidity and increased SARS-CoV-2 antibody compared to those COVID-19 individuals without neurological issues (CoV, n = 16). Protein markers of neuronal dysfunction including amyloid beta, neurofilament light, neurogranin, total tau, and p-T181-tau were all significantly increased in the nEVs of all participants recovering from COVID-19 compared to historic controls. This study suggests ongoing peripheral and neuroinflammation after COVID-19 infection that may influence neurological sequelae by altering nEV proteins. Individuals recovering from COVID-19 may have occult neural damage while those with demonstrative neurological symptoms additionally had more severe infection. Longitudinal studies to monitor plasma biomarkers and nEV cargo are warranted to assess persistent neurodegeneration and systemic effects. View Full-Text
Keywords: SARS-CoV-2; neurodegeneration; exosome; cytokines; comorbidities SARS-CoV-2; neurodegeneration; exosome; cytokines; comorbidities
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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MDPI and ACS Style

Sun, B.; Tang, N.; Peluso, M.J.; Iyer, N.S.; Torres, L.; Donatelli, J.L.; Munter, S.E.; Nixon, C.C.; Rutishauser, R.L.; Rodriguez-Barraquer, I.; Greenhouse, B.; Kelly, J.D.; Martin, J.N.; Deeks, S.G.; Henrich, T.J.; Pulliam, L. Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations. Cells 2021, 10, 386. https://doi.org/10.3390/cells10020386

AMA Style

Sun B, Tang N, Peluso MJ, Iyer NS, Torres L, Donatelli JL, Munter SE, Nixon CC, Rutishauser RL, Rodriguez-Barraquer I, Greenhouse B, Kelly JD, Martin JN, Deeks SG, Henrich TJ, Pulliam L. Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations. Cells. 2021; 10(2):386. https://doi.org/10.3390/cells10020386

Chicago/Turabian Style

Sun, Bing, Norina Tang, Michael J. Peluso, Nikita S. Iyer, Leonel Torres, Joanna L. Donatelli, Sadie E. Munter, Christopher C. Nixon, Rachel L. Rutishauser, Isabel Rodriguez-Barraquer, Bryan Greenhouse, John D. Kelly, Jeffrey N. Martin, Steven G. Deeks, Timothy J. Henrich, and Lynn Pulliam. 2021. "Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations" Cells 10, no. 2: 386. https://doi.org/10.3390/cells10020386

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