SARS-CoV-2 and Mitochondrial Proteins in Neural-Derived Exosomes of COVID-19.
Peluso. Michael J MJ; Deeks. Steven G SG; Mustapic. Maja M; Kapogiannis. Dimitrios D; Henrich. Timothy J TJ; Lu. Scott S; Goldberg. Sarah A SA; Hoh. Rebecca R; Chen. Jessica Y JY; Martinez. Enrique O EO; Kelly. J Daniel JD; Martin. Jeffrey N JN; Goetzl. Edward J EJ
Key Findings
- SARS‑CoV‑2 proteins are found in neuron‑ and astrocyte‑derived extracellular vesicles of long‑COVID patients
- Humanin (and MOTS‑c) levels are significantly reduced in neuron‑derived vesicles of patients with neuro‑psychiatric long‑COVID
- Other mitochondrial proteins show distinct patterns, with some decreasing only in neuro‑symptomatic patients and others increasing in astrocyte‑derived vesicles
Practical Outcomes
- The finding suggests monitoring humanin could help gauge brain‑related long‑COVID damage. Biohackers might consider strategies that boost mitochondrial health or humanin levels, but direct supplementation protocols are not yet proven and need more research.
Summary
The study shows that people with long‑COVID who have brain‑related symptoms have lower levels of the protective peptide humanin in tiny particles released from brain cells, suggesting a link between reduced humanin and neuro‑issues after COVID. While it doesn’t test any treatments, it points to humanin as a possible marker or target for helping brain health in long‑COVID.
Abstract
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. 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. 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. 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.
Study Information
pubmed
2022
2022-03-30T00:00:00.000Z
10.1002/ana.26350
92
41