{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T16:21:05Z","timestamp":1768494065562,"version":"3.49.0"},"posted":{"date-parts":[[2020,12,20]]},"group-title":"Immunology","reference-count":93,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2020,12,20]],"date-time":"2020-12-20T00:00:00Z","timestamp":1608422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,11,9]]},"abstract":"<jats:sec>\n                  <jats:title>Graphic abstract<\/jats:title>\n                  <jats:p>\n                    <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"423533v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                    <\/jats:fig>\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Summary<\/jats:title>\n                  <jats:p>Infections and neurodegenerative diseases induce neuroinflammation, but affected individuals often show a number of non-neural symptoms including muscle pain and muscle fatigue. The molecular pathways by which neuroinflammation causes pathologies outside the central nervous system (CNS) are poorly understood, so we developed three models to investigate the impact of neuroinflammation on muscle performance. We found that bacterial infection, COVID-like viral infection, and expression of a neurotoxic protein associated with Alzheimer\u2032 s disease promoted the accumulation of reactive oxygen species (ROS) in the brain. Excessive ROS induces the expression of the cytokine Unpaired 3 (Upd3) in insects, or its orthologue IL-6 in mammals, and CNS-derived Upd3\/IL-6 activates the JAK\/Stat pathway in skeletal muscle. In response to JAK\/Stat signaling, mitochondrial function is impaired and muscle performance is reduced. Our work uncovers a brain-muscle signaling axis in which infections and chronic diseases induce cytokine-dependent changes in muscle performance, suggesting IL-6 could be a therapeutic target to treat muscle weakness caused by neuroinflammation.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2020.12.20.423533","type":"posted-content","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T14:41:01Z","timestamp":1608648061000},"source":"Crossref","is-referenced-by-count":5,"title":["Infection and chronic disease activate a brain-muscle signaling axis that regulates muscle performance"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7929-0244","authenticated-orcid":false,"given":"Shuo","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0547-9447","authenticated-orcid":false,"given":"Meijie","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulong","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengyong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunyun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak","family":"Chhangani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany","family":"Ou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2933-646X","authenticated-orcid":false,"given":"Wenle","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ze","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"McAdow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego E.","family":"Rincon-Limas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanbo","family":"Tai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2783-5636","authenticated-orcid":false,"given":"Aaron","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024080505430023000_2020.12.20.423533v2.1","doi-asserted-by":"crossref","first-page":"14458","DOI":"10.1096\/fj.202000965RR","article-title":"Extramyocellular interleukin-6 influences skeletal muscle mitochondrial physiology through canonical JAK\/STAT signaling pathways","volume":"34","year":"2020","journal-title":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology"},{"key":"2024080505430023000_2020.12.20.423533v2.2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.111.132290"},{"key":"2024080505430023000_2020.12.20.423533v2.3","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1113\/JP281220","article-title":"JAK\/STAT inhibition augments soleus muscle function in a rat model of critical illness myopathy via regulation of complement C3\/3R","volume":"599","year":"2021","journal-title":"J Physiol"},{"key":"2024080505430023000_2020.12.20.423533v2.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.0133.x"},{"key":"2024080505430023000_2020.12.20.423533v2.5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-643544"},{"key":"2024080505430023000_2020.12.20.423533v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2006.08.003"},{"key":"2024080505430023000_2020.12.20.423533v2.7","first-page":"452","article-title":"Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. Lancet (London","volume":"400","year":"2022","journal-title":"England"},{"key":"2024080505430023000_2020.12.20.423533v2.8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jneuroim.2014.05.003","article-title":"Neonatal Escherichia coli K1 meningitis causes learning and memory impairments in adulthood","volume":"272","year":"2014","journal-title":"Journal of neuroimmunology"},{"key":"2024080505430023000_2020.12.20.423533v2.9","unstructured":"Beckman, D. , Bonillas, A. , Diniz, G.B. , et al., SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19. Cell Reports."},{"key":"2024080505430023000_2020.12.20.423533v2.10","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1111\/jgs.17206","article-title":"Sarcopenia is associated with incident Alzheimer\u2019s dementia, mild cognitive impairment, and cognitive decline","volume":"69","year":"2021","journal-title":"Journal of the American Geriatrics Society"},{"key":"2024080505430023000_2020.12.20.423533v2.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00524-3"},{"key":"2024080505430023000_2020.12.20.423533v2.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03756-0"},{"key":"2024080505430023000_2020.12.20.423533v2.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1306220110"},{"key":"2024080505430023000_2020.12.20.423533v2.14","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1126\/science.abn0910","article-title":"Liver-heart cross-talk mediated by coagulation factor XI protects against heart failure","volume":"377","year":"2022","journal-title":"Science"},{"key":"2024080505430023000_2020.12.20.423533v2.15","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr100"},{"key":"2024080505430023000_2020.12.20.423533v2.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.04.019"},{"key":"2024080505430023000_2020.12.20.423533v2.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.10.006"},{"key":"2024080505430023000_2020.12.20.423533v2.18","doi-asserted-by":"crossref","unstructured":"Chen, Z. , Li, B. , Zhan, R.Z. , et al., 2021b. Exercise mimetics and JAK inhibition attenuate IFN-gamma-induced wasting in engineered human skeletal muscle. Sci Adv 7.","DOI":"10.1126\/sciadv.abd9502"},{"key":"2024080505430023000_2020.12.20.423533v2.19","doi-asserted-by":"crossref","unstructured":"Chiu, J.C. , Low, K.H. , Pike, D.H. , et al., 2010. Assaying locomotor activity to study circadian rhythms and sleep parameters in Drosophila. J Vis Exp.","DOI":"10.3791\/2157"},{"key":"2024080505430023000_2020.12.20.423533v2.20","doi-asserted-by":"crossref","first-page":"e2200960119","DOI":"10.1073\/pnas.2200960119","article-title":"Morphological, cellular, and molecular basis of brain infection in COVID-19 patients","volume":"119","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024080505430023000_2020.12.20.423533v2.21","doi-asserted-by":"crossref","first-page":"104131","DOI":"10.1016\/j.archger.2020.104131","article-title":"The relationship between interleukin-6 levels and physical performance in mobility-limited older adults with chronic low-grade inflammation: The ENRGISE Pilot study","volume":"90","year":"2020","journal-title":"Arch Gerontol Geriatr"},{"key":"2024080505430023000_2020.12.20.423533v2.22","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1007\/s10787-021-00889-6","article-title":"Recent advances in molecular pathways and therapeutic implications targeting neuroinflammation for Alzheimer\u2019s disease","volume":"29","year":"2021","journal-title":"Inflammopharmacology"},{"key":"2024080505430023000_2020.12.20.423533v2.23","doi-asserted-by":"crossref","first-page":"109553","DOI":"10.1016\/j.celrep.2021.109553","article-title":"Coordination of tumor growth and host wasting by tumor-derived Upd3","volume":"36","year":"2021","journal-title":"Cell Rep"},{"key":"2024080505430023000_2020.12.20.423533v2.24","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/s41586-022-04569-5","article-title":"SARS-CoV-2 is associated with changes in brain structure in UK Biobank","volume":"604","year":"2022","journal-title":"Nature"},{"key":"2024080505430023000_2020.12.20.423533v2.25","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1038\/s41467-021-22599-x","article-title":"Proteomics of protein trafficking by in vivo tissue-specific labeling","volume":"12","year":"2021","journal-title":"Nature communications"},{"key":"2024080505430023000_2020.12.20.423533v2.26","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1123\/jsr.2016-0107","article-title":"Regeneration of Skeletal Muscle After Eccentric Injury","volume":"26","year":"2017","journal-title":"Journal of sport rehabilitation"},{"key":"2024080505430023000_2020.12.20.423533v2.27","doi-asserted-by":"crossref","first-page":"680858","DOI":"10.3389\/fncel.2021.680858","article-title":"Neuronal Damage and Neuroinflammation, a Bridge Between Bacterial Meningitis and Neurodegenerative Diseases","volume":"15","year":"2021","journal-title":"Front Cell Neurosci"},{"key":"2024080505430023000_2020.12.20.423533v2.28","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1016\/j.cell.2022.06.008","article-title":"Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation","volume":"185","year":"2022","journal-title":"Cell"},{"key":"2024080505430023000_2020.12.20.423533v2.29","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E15-07-0546"},{"key":"2024080505430023000_2020.12.20.423533v2.30","doi-asserted-by":"crossref","unstructured":"Frere, J.J. , Serafini, R.A. , Pryce, K.D. , et al., 2022. SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery. Sci Transl Med 14, eabq3059.","DOI":"10.1126\/scitranslmed.abq3059"},{"key":"2024080505430023000_2020.12.20.423533v2.31","doi-asserted-by":"crossref","first-page":"eabj4991","DOI":"10.1126\/sciadv.abj4991","article-title":"Physiological ROS controls Upd3-dependent modeling of ECM to support cardiac function in Drosophila","volume":"8","year":"2022","journal-title":"Sci Adv"},{"key":"2024080505430023000_2020.12.20.423533v2.32","doi-asserted-by":"crossref","first-page":"11290","DOI":"10.1038\/s41598-022-15578-9","article-title":"Altered mitochondrial microenvironment at the spotlight of musculoskeletal aging and Alzheimer\u2019s disease","volume":"12","year":"2022","journal-title":"Scientific reports"},{"key":"2024080505430023000_2020.12.20.423533v2.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.016"},{"key":"2024080505430023000_2020.12.20.423533v2.34","doi-asserted-by":"publisher","DOI":"10.2337\/diab.10.3.232"},{"key":"2024080505430023000_2020.12.20.423533v2.35","doi-asserted-by":"crossref","first-page":"155496","DOI":"10.1016\/j.cyto.2021.155496","article-title":"Glycyrrhizin prevents SARS-CoV-2 S1 and Orf3a induced high mobility group box 1 (HMGB1) release and inhibits viral replication","volume":"142","year":"2021","journal-title":"Cytokine"},{"key":"2024080505430023000_2020.12.20.423533v2.36","first-page":"57","article-title":"Circulating Interleukin-6 Is Associated with Skeletal Muscle Strength, Quality, and Functional Adaptation with Exercise Training in Mobility-Limited Older Adults","volume":"9","year":"2020","journal-title":"J Frailty Aging"},{"key":"2024080505430023000_2020.12.20.423533v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/nature07151"},{"key":"2024080505430023000_2020.12.20.423533v2.38","unstructured":"Haq, M. , Adnan, G. , 2022. Ruxolitinib., StatPearls [Internet]. StatPearls Publishing, Treasure Island (FL), p. https:\/\/https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK570600\/."},{"key":"2024080505430023000_2020.12.20.423533v2.39","doi-asserted-by":"crossref","unstructured":"Harsh, S. , Fu, Y. , Kenney, E. , et al., 2020. Zika virus non-structural protein NS4A restricts eye growth in Drosophila through regulation of JAK\/STAT signaling. Dis Model Mech 13.","DOI":"10.1242\/dmm.040816"},{"key":"2024080505430023000_2020.12.20.423533v2.40","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1016\/j.bbadis.2015.03.012","article-title":"Altered ROS production, NF-kappaB activation and interleukin-6 gene expression induced by electrical stimulation in dystrophic mdx skeletal muscle cells","volume":"1852","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"2024080505430023000_2020.12.20.423533v2.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0244-7"},{"key":"2024080505430023000_2020.12.20.423533v2.42","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32656-8"},{"key":"2024080505430023000_2020.12.20.423533v2.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2011.11.016"},{"key":"2024080505430023000_2020.12.20.423533v2.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.05.003"},{"key":"2024080505430023000_2020.12.20.423533v2.45","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s40478-021-01264-w","article-title":"TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer\u2019s disease hippocampus","volume":"9","year":"2021","journal-title":"Acta Neuropathol Commun"},{"key":"2024080505430023000_2020.12.20.423533v2.46","doi-asserted-by":"publisher","DOI":"10.1242\/dev.071464"},{"key":"2024080505430023000_2020.12.20.423533v2.47","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41594-021-00619-0","article-title":"Cryo-EM structure of SARS-CoV-2 ORF3a in lipid nanodiscs","volume":"28","year":"2021","journal-title":"Nature structural & molecular biology"},{"key":"2024080505430023000_2020.12.20.423533v2.48","doi-asserted-by":"crossref","unstructured":"Khomich, O.A. , Kochetkov, S.N. , Bartosch, B. , et al., 2018. Redox Biology of Respiratory Viral Infections. Viruses 10.","DOI":"10.3390\/v10080392"},{"key":"2024080505430023000_2020.12.20.423533v2.49","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1952"},{"key":"2024080505430023000_2020.12.20.423533v2.50","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70306-8"},{"key":"2024080505430023000_2020.12.20.423533v2.51","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316201"},{"key":"2024080505430023000_2020.12.20.423533v2.52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409427111"},{"key":"2024080505430023000_2020.12.20.423533v2.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.12.012"},{"key":"2024080505430023000_2020.12.20.423533v2.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.01.005"},{"key":"2024080505430023000_2020.12.20.423533v2.55","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?","volume":"17","year":"2021","journal-title":"Nat Rev Neurol"},{"key":"2024080505430023000_2020.12.20.423533v2.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.022"},{"key":"2024080505430023000_2020.12.20.423533v2.57","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1007\/s00277-020-04243-8","article-title":"Ruxolitinib treatment improves muscle mass in patients with myelofibrosis","volume":"100","year":"2021","journal-title":"Annals of hematology"},{"key":"2024080505430023000_2020.12.20.423533v2.58","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw878"},{"key":"2024080505430023000_2020.12.20.423533v2.59","first-page":"46","article-title":"[Inflammatory myopathy following acute meningoccemia in a properdin-deficient patient: A case report]","volume":"41","year":"2020","journal-title":"La Revue de medecine interne"},{"key":"2024080505430023000_2020.12.20.423533v2.60","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/00075197-200103000-00011","article-title":"Dissecting the energy needs of the body","volume":"4","year":"2001","journal-title":"Current Opinion in Clinical Nutrition & Metabolic Care"},{"key":"2024080505430023000_2020.12.20.423533v2.61","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/00075197-200103000-00011","article-title":"Dissecting the energy needs of the body","volume":"4","year":"2001","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"2024080505430023000_2020.12.20.423533v2.62","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170600"},{"key":"2024080505430023000_2020.12.20.423533v2.63","doi-asserted-by":"crossref","first-page":"500","DOI":"10.3389\/fphys.2019.00500","article-title":"The JAK\/STAT Pathway in Skeletal Muscle Pathophysiology","volume":"10","year":"2019","journal-title":"Front Physiol"},{"key":"2024080505430023000_2020.12.20.423533v2.64","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12632-5"},{"key":"2024080505430023000_2020.12.20.423533v2.65","doi-asserted-by":"crossref","unstructured":"Morris, J.K. , McCoin, C.S. , Fuller, K.N. , et al., 2021. Mild Cognitive Impairment and Donepezil Impact Mitochondrial Respiratory Capacity in Skeletal Muscle. Function (Oxford, England) 2, zqab045.","DOI":"10.1093\/function\/zqab045"},{"key":"2024080505430023000_2020.12.20.423533v2.66","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2820"},{"key":"2024080505430023000_2020.12.20.423533v2.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25015-6"},{"key":"2024080505430023000_2020.12.20.423533v2.68","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.cmet.2021.03.005","article-title":"Proteasome stress in skeletal muscle mounts a long-range protective response that delays retinal and brain aging","volume":"33","year":"2021","journal-title":"Cell Metab"},{"key":"2024080505430023000_2020.12.20.423533v2.69","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1126\/science.aag2590","article-title":"How neuroinflammation contributes to neurodegeneration. Science (New York","volume":"353","year":"2016","journal-title":"N.Y"},{"key":"2024080505430023000_2020.12.20.423533v2.70","doi-asserted-by":"publisher","DOI":"10.1101\/gad.329110.119"},{"key":"2024080505430023000_2020.12.20.423533v2.71","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.10.017"},{"key":"2024080505430023000_2020.12.20.423533v2.72","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005595"},{"key":"2024080505430023000_2020.12.20.423533v2.73","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5629-08.2009"},{"key":"2024080505430023000_2020.12.20.423533v2.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111143"},{"key":"2024080505430023000_2020.12.20.423533v2.75","unstructured":"Song, E. , Zhang, C. , Israelow, B. , et al., 2021. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med 218."},{"key":"2024080505430023000_2020.12.20.423533v2.76","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nrrheum.2017.172","article-title":"The brain and immune system prompt energy shortage in chronic inflammation and ageing","volume":"13","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"2024080505430023000_2020.12.20.423533v2.77","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1038\/s41591-022-01909-w","article-title":"Symptoms and risk factors for long COVID in non-hospitalized adults","volume":"28","year":"2022","journal-title":"Nature medicine"},{"key":"2024080505430023000_2020.12.20.423533v2.78","doi-asserted-by":"crossref","first-page":"e199","DOI":"10.1038\/tp.2012.120","article-title":"Evidence for sustained elevation of IL-6 in the CNS as a key contributor of depressive-like phenotypes","volume":"2","year":"2012","journal-title":"Transl Psychiatry"},{"key":"2024080505430023000_2020.12.20.423533v2.79","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1016\/j.ajpath.2020.04.013","article-title":"The Unraveling: Cardiac and Musculoskeletal Defects and Their Role in Common Alzheimer Disease Morbidity and Mortality","volume":"190","year":"2020","journal-title":"Am J Pathol"},{"key":"2024080505430023000_2020.12.20.423533v2.80","doi-asserted-by":"crossref","unstructured":"Swank, Z. , Senussi, Y. , Manickas-Hill, Z. , et al., 2022. Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.","DOI":"10.1101\/2022.06.14.22276401"},{"key":"2024080505430023000_2020.12.20.423533v2.81","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S2215-0366(21)00084-5","article-title":"6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records","volume":"8","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"2024080505430023000_2020.12.20.423533v2.82","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1038\/s41467-022-30836-0","article-title":"Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records","volume":"13","year":"2022","journal-title":"Nat Commun"},{"key":"2024080505430023000_2020.12.20.423533v2.83","doi-asserted-by":"crossref","first-page":"102608","DOI":"10.1016\/j.conb.2022.102608","article-title":"Neuroinflammation and COVID-19","volume":"76","year":"2022","journal-title":"Current opinion in neurobiology"},{"key":"2024080505430023000_2020.12.20.423533v2.84","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3691"},{"key":"2024080505430023000_2020.12.20.423533v2.85","doi-asserted-by":"crossref","unstructured":"Watson, A.S. , Soilleux, E.J. , 2015. Detection of p62 on Paraffin Sections by Immunohistochemistry. Cold Spring Harb Protoc 2015, 756\u2013760.","DOI":"10.1101\/pdb.prot086280"},{"key":"2024080505430023000_2020.12.20.423533v2.86","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.153"},{"key":"2024080505430023000_2020.12.20.423533v2.87","doi-asserted-by":"crossref","unstructured":"Xu, E. , Xie, Y. , Al-Aly, Z ., 2022. Long-term neurologic outcomes of COVID-19. Nature medicine.","DOI":"10.1038\/s41467-023-36223-7"},{"key":"2024080505430023000_2020.12.20.423533v2.88","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03710"},{"key":"2024080505430023000_2020.12.20.423533v2.89","doi-asserted-by":"crossref","unstructured":"Yang, S. , Yu, J. , Fan, Z. , et al., 2018. Bub1 Facilitates Virus Entry through Endocytosis in a Model of Drosophila Pathogenesis. J Virol 92.","DOI":"10.1128\/JVI.00254-18"},{"key":"2024080505430023000_2020.12.20.423533v2.90","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.chom.2019.07.001","article-title":"Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediate Local-Systemic Innate Immune Communication in Drosophila","volume":"26","year":"2019","journal-title":"Cell Host Microbe"},{"key":"2024080505430023000_2020.12.20.423533v2.91","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/jcsm.12867","article-title":"Sepsis induces interleukin 6, gp130\/JAK2\/STAT3, and muscle wasting","volume":"13","year":"2022","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"2024080505430023000_2020.12.20.423533v2.92","doi-asserted-by":"crossref","first-page":"854567","DOI":"10.3389\/fmicb.2022.854567","article-title":"Understanding the Role of SARS-CoV-2 ORF3a in Viral Pathogenesis and COVID-19","volume":"13","year":"2022","journal-title":"Frontiers in microbiology"},{"key":"2024080505430023000_2020.12.20.423533v2.93","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2019.4188"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2020.12.20.423533","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T01:10:34Z","timestamp":1768439434000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2020.12.20.423533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,20]]},"references-count":93,"URL":"https:\/\/doi.org\/10.1101\/2020.12.20.423533","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1126\/sciimmunol.adm7908","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2020,12,20]]},"subtype":"preprint"}}