Inflammation from mild COVID-19 results in persistent neurological and behavioral changes in rhesus macaques

Inflammation from mild COVID-19 results in persistent neurological and behavioral changes in rhesus macaques | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Inflammation from mild COVID-19 results in persistent neurological and behavioral changes in rhesus macaques Tomas R Wiche Salinas, Sienna Freeman, Rebecca Richardson, Winni Weng, and 20 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8159193/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Although most SARS-CoV-2 infections result in mild or moderate symptoms not requiring hospitalization, many patients experience persistent symptoms after their initial recovery, a condition termed Post-Acute Sequelae of SARS-CoV-2 infection (PASC). The underlying pathogenesis behind infection associated chronic illnesses, such as PASC, are poorly understood, thus critically limiting the development of therapeutics to prevent or alleviate symptoms. The current study examined the neurocognitive impact of SARS-CoV-2 induced inflammation in a nonhuman primate model. Ten adult rhesus macaques (5 female, 5 male) were monitored before, during, and after recovery from a mild COVID-19 illness (SARS-CoV-2 strain 2019-noCoV/USA-WA1/2020). Macaques exhibited persistent alterations in taste and smell, as well as decreased cognitive flexibility up to 3 months post-infection. Female macaques experienced sleep disturbances, greater stress and poorer autonomic function months after SARS-CoV-2 infection. Importantly, the development of these neurocognitive changes were associated with acute cytokine response to infection and increased microglia activation in brain tissue at 4 months post-infection. These findings suggest a causative link between the inflammatory response to mild COVID-19 symptoms and persistent neurocognitive changes associated with PASC and provide rationale for therapeutic strategies aimed at reducing acute inflammatory responses to the virus. Infectious Diseases Cognitive Neuroscience Neurobiology of Disease PASC Long-COVID Neuroinflammation Nonhuman primate Sex differences Heart rate variability Full Text Additional Declarations The authors declare no competing interests. All procedures in this study were approved by the Emory University Institutional Animal Care and Use Committee and were conducted in an AAALAC accredited facility in full compliance with the United States Public Health Service Policy on Humane Care and use of Laboratory Animals. Supplementary Files NHPPASCSupplementaryfigures112125.pdf Supplementary Figures Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8159193","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":547800188,"identity":"4e5bf3c6-4291-4932-83f7-cfc46ed929e4","order_by":0,"name":"Tomas R Wiche Salinas","email":"","orcid":"","institution":"Emory National Primate Research Center","correspondingAuthor":false,"prefix":"","firstName":"Tomas","middleName":"R Wiche","lastName":"Salinas","suffix":""},{"id":547800189,"identity":"947274e6-a91e-4c91-96e7-4648795789c1","order_by":1,"name":"Sienna Freeman","email":"","orcid":"","institution":"Emory National Primate Research 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