{"doi":"10.1002/ana.26350","title":"SARS‐CoV‐2 and Mitochondrial Proteins in Neural‐Derived Exosomes of COVID‐19","abstract":"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.","journal":"Annals of Neurology","year":2022,"id":233617,"datarank":0.7206031567099886,"base_score":4.804021044733257,"endowment":4.804021044733257,"self_citation_contribution":0.7206031567099886,"citation_network_contribution":0.0,"self_endowment_contribution":0.7206031567099886,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":121,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7079,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":71691,"name":"Steven G. Deeks","orcid":"0000-0001-6371-747X","position":1,"is_corresponding":false},{"id":304883,"name":"Maja Mustapić","orcid":"0000-0003-0511-2047","position":2,"is_corresponding":false},{"id":256661,"name":"Dimitrios Kapogiannis","orcid":"0000-0003-2181-3118","position":3,"is_corresponding":false},{"id":239686,"name":"Timothy J. Henrich","orcid":"0000-0002-6684-0622","position":4,"is_corresponding":false},{"id":619680,"name":"Scott Lu","orcid":null,"position":5,"is_corresponding":false},{"id":618496,"name":"Sarah A. Goldberg","orcid":"0000-0002-8642-1468","position":6,"is_corresponding":false},{"id":71690,"name":"Rebecca Hoh","orcid":"0000-0001-5112-4220","position":7,"is_corresponding":false},{"id":401605,"name":"Jessica Y. Chen","orcid":"0000-0002-4833-6756","position":8,"is_corresponding":false},{"id":637651,"name":"Enrique Ortega Martínez","orcid":null,"position":9,"is_corresponding":false},{"id":252180,"name":"J. Daniel Kelly","orcid":"0000-0002-7616-0321","position":10,"is_corresponding":false},{"id":239684,"name":"Jeffrey N. Martin","orcid":"0000-0002-9773-3256","position":11,"is_corresponding":false},{"id":281925,"name":"Edward J. Goetzl","orcid":"0000-0002-0706-5371","position":12,"is_corresponding":false},{"id":228705,"name":"Michael J. Peluso","orcid":"0000-0003-0585-6230","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:21:31.237180Z","pmid":"35285072","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}