Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations
Bing Sun,
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,
Lynn Pulliam
Affiliations
Bing Sun
Department of Laboratory Medicine, San Francisco VA Health Care System, San Francisco, CA 94121, USA
Norina Tang
Department of Laboratory Medicine, San Francisco VA Health Care System, San Francisco, CA 94121, USA
Michael J. Peluso
Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
Nikita S. Iyer
Division of Experimental Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
Leonel Torres
Division of Experimental Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
Joanna L. Donatelli
Division of Experimental Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
Sadie E. Munter
Division of Experimental Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
Christopher C. Nixon
Division of Experimental Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
Rachel L. Rutishauser
Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
Isabel Rodriguez-Barraquer
Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
Bryan Greenhouse
Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
John D. Kelly
Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA 94158, USA
Jeffrey N. Martin
Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA 94158, USA
Steven G. Deeks
Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
Timothy J. Henrich
Division of Experimental Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94110, USA
Lynn Pulliam
Department of Laboratory Medicine, San Francisco VA Health Care System, San Francisco, CA 94121, USA
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.
