Vitamin B12 and D deficiency as cofactors of COVID-19 vaccine-induced chronic neurological adverse reactions: Two cases and a hypothesis

Vitamin B12 and D deficiency as cofactors of COVID-19 vaccine-induced chronic neurological adverse reactions: Two cases and a hypothesis | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Vitamin B12 and D deficiency as cofactors of COVID-19 vaccine-induced chronic neurological adverse reactions: Two cases and a hypothesis Harriet Amy Carroll, Ewen Millar, Kevin Alexander Deans This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1425014/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Background: The COVID-19 vaccines have been an essential measure to help reduce COVID-19-related injury and death. However, in some cases, vaccination has caused severe and chronic reactions, akin to post-acute sequelae of COVID-19 (long COVID). Cases: In Version 1 of this manuscript, we presented two cases (Case 1: male, age 43 years, Pfizer BNT162b2 vaccination; Case 2: female, age 30 years, Oxford-AstraZeneca ChAdOx1nCoV-19 vaccination) with severe neurological adverse reaction post-vaccine and concomitant vitamin B12 deficiency. Both cases presented with non-textbook symptomatology of vitamin B12 deficiency. Case 1 had full symptom resolution with vitamin B12 replacement therapy, including after a second vaccine whereby symptoms returned. In Case 2, frank vitamin D deficiency and chronically elevated D-dimer were also found. Here we elaborate on further tests done on Case 2 only. Upon additional investigation due to significantly incomplete recovery with B12 and vitamin D replacement, Case 2 was diagnosed with a vaccine-induced long COVID-like syndrome, with evidence of microclots and perfusion imaging that was diffusely abnormal with widespread small defects, some areas of which were mismatched to ventilation, reported as possibly due to small pulmonary emboli; as well as mast cell activation syndrome; postural orthostatic tachycardia syndrome and dysautonomia; endocrine dysfunction; and worsened myalgic encephalomyelitis. Additionally, homocysteine remained elevated even after extensive B12 replacement, requiring folic acid supplementation despite no evidence of relevant genetic variants. Discussion: Vaccines, including the COVID-19 vaccines, are known to cause severe and/or chronic neurological reactions in some cases. We support research into screening for vitamin B12 deficiency prior to vaccination in high-risk groups (e.g. those following an animal produce free diet), those suffering atypical/chronic vaccine reactions, and those with similar conditions, such as post-acute sequelae of COVID-19 (long COVID). Here we demonstrate (to our knowledge) the first in-depth clinical exploration of a long COVID-like syndrome—in this case induced from vaccination—using established clinical pathways to make multiple diagnoses. Key lessons for clinicians seeing patients with (vaccine- or infection-induced) long COVID-like symptoms are: breathlessness should not be assumed to be dysautonomia, rather clotting should be fully explored; check for autonomic nervous system dysfunction; check for signs of mast cell activation syndrome and myalgic encephalomyelitis; and be aware that leaving these pathologies untreated can seemingly cause ongoing endocrine and metabolic dysfunction. Clinical and scientific investigation is warranted to understand how these pathologies interact in order to identify optimum treatment targets on a case-by-case basis. Case 2 is continuing to be monitored and the paper will be updated accordingly if necessary. Pathology aldosterone arginine vasopressin cobalamin copeptin COVID-19 vaccine deficiency demyelination dysautonomia vaccine-induced long COVID MCAS MTHFR neuropathy post-acute sequelae of COVID-19 POTS serious adverse events vaccine injuries vitamin B12 vitamin D Full Text Additional Declarations The authors declare potential competing interests as follows: KAD has received speaking honoraria from Amgen, NAPP and AstraZeneca in the past ten years. HAC, CD, OD, and ECM declare no conflicts of interest. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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 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-1425014","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":89282405,"identity":"b2a06473-c9db-4196-a094-df90250d241a","order_by":0,"name":"Harriet Amy Carroll","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBklEQVRIie3RsUrEMBjA8S8EmqVQx5SCvkJKoeehD9Pi0EnQRTKFHIHc0geoD+F6cyVgl+Dc9bjB9caCDtrTHi65u1Ew/ykh+ZGEAPh8fzAGaLEZOD3/GgfjFIBMK06CVQb2MpsIBXyUEJ0gzUu5I3ACmZFnmdxrWj01RbDhd0JEGNB2AJO5yLwuZda80ttVX5DUMkNjBTiuweTOi/VIFuHDjgSxZC1lBiABMNeHSBsGtMq/iRgJfj9CFirUtPgheCTBeIr7YrZUqLE0Xdn1MpXMxI8K6XnNKufzWde9DVsuLvLu5mUtP0QUEWX6gV+l0mX2nZXTHiQP/MrvovaUXT6fz/cf+wSjQVOJoxZLsgAAAABJRU5ErkJggg==","orcid":"","institution":"NHS Grampian","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Harriet","middleName":"Amy","lastName":"Carroll","suffix":""},{"id":89282406,"identity":"a9ed481e-a340-4a86-9a11-43e3de20e91b","order_by":1,"name":"Ewen Millar","email":"","orcid":"","institution":"NHS Grampian","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ewen","middleName":"","lastName":"Millar","suffix":""},{"id":89282407,"identity":"537525c4-4319-4225-a5e8-85c40134d227","order_by":2,"name":"Kevin Alexander Deans","email":"","orcid":"","institution":"NHS Grampian","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"Alexander","lastName":"Deans","suffix":""}],"badges":[],"createdAt":"2022-03-06 19:52:27","currentVersionCode":2,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false,"coiExplicitlySet":false},"doi":"10.21203/rs.3.rs-1425014/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-1425014/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106414824,"identity":"6b7a5760-4397-4141-8dc2-6bb661557fff","added_by":"auto","created_at":"2026-04-08 10:25:28","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":470937,"visible":true,"origin":"","legend":"","description":"","filename":"Carrolletal.2026B12updatev2.1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1425014/v2_covered_501f6e96-33ac-428d-a515-4c12df85e55c.pdf"}],"financialInterests":"The authors declare potential competing interests as follows: KAD has received speaking honoraria from Amgen, NAPP and AstraZeneca in the past ten years. 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","formattedTitle":"\u003cp\u003eVitamin B12 and D deficiency as cofactors of COVID-19 vaccine-induced chronic neurological adverse reactions: Two cases and a hypothesis\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"NHS Grampian","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"aldosterone; arginine vasopressin; cobalamin; copeptin; COVID-19 vaccine; deficiency; demyelination; dysautonomia; vaccine-induced long COVID; MCAS; MTHFR; neuropathy; post-acute sequelae of COVID-19; POTS; serious adverse events; vaccine injuries; vitamin B12; vitamin D","lastPublishedDoi":"10.21203/rs.3.rs-1425014/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1425014/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThe COVID-19 vaccines have been an essential measure to help reduce COVID-19-related injury and death. However, in some cases, vaccination has caused severe and chronic reactions, akin to post-acute sequelae of COVID-19 (long COVID).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCases: \u003c/strong\u003eIn Version 1 of this manuscript, we presented two cases (Case 1: male, age 43 years, Pfizer BNT162b2 vaccination; Case 2: female, age 30 years, Oxford-AstraZeneca ChAdOx1nCoV-19 vaccination) with severe neurological adverse reaction post-vaccine and concomitant vitamin B12 deficiency. Both cases presented with non-textbook symptomatology of vitamin B12 deficiency. Case 1 had full symptom resolution with vitamin B12 replacement therapy, including after a second vaccine whereby symptoms returned. In Case 2, frank vitamin D deficiency and chronically elevated D-dimer were also found. Here we elaborate on further tests done on Case 2 only. 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We support research into screening for vitamin B12 deficiency prior to vaccination in high-risk groups (e.g. those following an animal produce free diet), those suffering atypical/chronic vaccine reactions, and those with similar conditions, such as post-acute sequelae of COVID-19 (long COVID). Here we demonstrate (to our knowledge) the first in-depth clinical exploration of a long COVID-like syndrome—in this case induced from vaccination—using established clinical pathways to make multiple diagnoses. Key lessons for clinicians seeing patients with (vaccine- or infection-induced) long COVID-like symptoms are: breathlessness should not be assumed to be dysautonomia, rather clotting should be fully explored; check for autonomic nervous system dysfunction; check for signs of mast cell activation syndrome and myalgic encephalomyelitis; and be aware that leaving these pathologies untreated can seemingly cause ongoing endocrine and metabolic dysfunction. Clinical and scientific investigation is warranted to understand how these pathologies interact in order to identify optimum treatment targets on a case-by-case basis. Case 2 is continuing to be monitored and the paper will be updated accordingly if necessary.\u003c/p\u003e","manuscriptTitle":"Vitamin B12 and D deficiency as cofactors of COVID-19 vaccine-induced chronic neurological adverse reactions: Two cases and a hypothesis","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2026-04-03 16:59:20","doi":"10.21203/rs.3.rs-1425014/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2022-03-08 21:42:13","doi":"10.21203/rs.3.rs-1425014/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"90393ee9-6eec-4745-a194-3566ec6f96ba","owner":[],"postedDate":"April 3rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":10931249,"name":"Pathology"}],"tags":[],"updatedAt":"2022-03-08T21:42:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-03 16:59:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-1425014","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1425014","identity":"rs-1425014","version":["v2"]},"buildId":"PRX_uewTKcrkEM4liVh3c","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}