Annals of neurologyMar 14, 2022

SARS-CoV-2 and Mitochondrial Proteins Found in Brain Cell Tiny Particles of COVID-19 Patients

Updated Apr 6, 2026

Abstract

Mean levels of SARS-CoV-2 N protein were higher in post-acute sequelae of SARS-CoV-2 (PASC) patients with neuropsychiatric manifestations compared to those without.

SARS-CoV-2 S1 and nucleocapsid proteins were elevated in all PASC sub-groups compared to healthy controls.
Subunit 6 of mitochondrial respiratory chain complex I and subunit 10 of complex III levels were significantly lower in PASC with neuropsychiatric manifestations.
Neuroprotective mitochondrial proteins Humanin and MOTS-c showed decreased levels in PASC with neuropsychiatric manifestations compared to controls.
Levels of voltage-dependent anion-selective channel protein 1 and N-methyl-D-aspartate receptor 1 were reduced in both PASC groups.
Calcium channel proteins were decreased only in PASC patients with neuropsychiatric manifestations.

Simplified

OBJECTIVE: As SARS-CoV-2 is known to invade neural cell mitochondria, a plasma system for quantifying central nervous system proteins in living humans was used to investigate neuropathogenic mechanisms of long-COVID-19.

METHODS: SARS-CoV-2 proteins and mitochondrial proteins (MPs) in enriched plasma neuron-derived extracellular vesicles (NDEVs) and astrocyte-derived EVs (ADEVs) were quantified in resolved acute COVID-19 without post-acute sequelae of SARS-CoV-2 (PASC), PASC without neuropsychiatric manifestations (NP), PASC with NP and healthy controls.

RESULTS: NDEV and ADEV mean levels of SARS-CoV-2 S1 and nucleocapsid (N) proteins were higher in all PASC sub-groups than controls, but only N levels were higher in PASC with than without NP. Exosome marker CD81-normalized NDEV mean levels of subunit 6 of MP respiratory chain complex I and subunit 10 of complex III, and neuroprotective MPs Humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were decreased significantly in PASC with NP but not in PASC without NP relative to controls. NDEV levels of MPs voltage-dependent anion-selective channel protein 1 (VDAC1) and N-methyl-D-aspartate receptor 1 (NMDAR1) were decreased in PASC without and with NP, whereas those of calcium channel MPs mitochondrial calcium uniporter (MCU), sodium/calcium exchanger (NCLX) and leucine zipper EF-hand containing transmembrane 1 protein (LETM1) were decreased only in PASC with NP. ADEV levels of MCU and NCLX only were increased in PASC without and with NP.

INTERPRETATION: Abnormal NDEV and ADEV levels of SARS-CoV-2 N and S1 protein and MPs correlate with NP and may be biomarkers for long-COVID prognostics and therapeutic trials. ANN NEUROL 2022;91:772-781.

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Competing interests

No authors declare any conflict‐of‐interest except for Dr. Goetzl who has filed an application covering this lab methodology with the US Patent and Trademark Office.

PubMed

SARS-CoV-2 and Mitochondrial Proteins Found in Brain Cell Tiny Particles of COVID-19 Patients

Abstract

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Competing interests

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Abstract

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Funding

Competing interests

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You found one interesting study. We’ll send the next 7.

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Recent issues from the long covid brief