Case Report 1: NAD+ Oscillation Therapy (NOT) to treat Covid-19 aggravated by poorly controlled Diabetes Melitus Type 2

Case Report 1: NAD+ Oscillation Therapy (NOT) to treat Covid-19 aggravated by poorly controlled Diabetes Melitus Type 2 | 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 Case Report Case Report 1: NAD+ Oscillation Therapy (NOT) to treat Covid-19 aggravated by poorly controlled Diabetes Melitus Type 2 Adriaan Francois van Wyk, Theo Verwey This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-123044/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 We report on a case of a 50 year old diabetic, obese and hypertensive male patient that developed severe disease, was admitted and treated with NAD+ Oscillation Therapy (NOT) and then discharged in a stable condition within 5 days (not requiring home oxygen therapy). In addition to the favourable outcome in regards to severe COVID-19 disease, the patient’s blood glucose levels were better controlled after resolution of COVID-19 and the patient has no apparent post-COVID-19 morbidity, which has been reported in countries across the world. NAD+ Oscillation Therapy is a novel medical treatment developed in South Africa. NAD+ Oscillation Therapy envelops the real time measurement of the NAD+/NADH ratio and modulation of the ratio with the goal of restoration of homeostasis. This supports the primary role of the immune system which is protection and restoration. This case shows a favourable treatment outcome in a high risk patient that developed severe disease. Treatment was initiated early and hospitalization was done before laboratory markers reached critical levels. This case highlights the importance of early treatment initiation, effective patient counselling re home care (recognition of sepsis and respiratory distress), NOT as a realtime treatment method of sepsis and the advantage of NOT as a treatment modality in COVID-19 patient care. Infectious Diseases NAD+ Oscillation Therapy (NOT) COVID-19 Diabetes Mellitus Type 2 Hypertension Nicotinamide Adenine Dinucleotide (NAD+) Reduced Nicotinamide Adenine Dinucleotide (NADH) Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Full Text Declarations DECLARATION OF CONSENT: We hereby declare that the patient consented to publication of his anonymised clinical data, as well as the patient perspective. Written consent has been obtained. 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-123044","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":5939652,"identity":"ab128c61-b14c-4bea-9058-a58bd347db6d","order_by":0,"name":"Adriaan Francois van Wyk","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-5146-4134","institution":"Private Practice","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Adriaan","middleName":"Francois van","lastName":"Wyk","suffix":""},{"id":5939653,"identity":"906ddbf9-f2af-4818-a6d1-fc4449fcd154","order_by":1,"name":"Theo Verwey","email":"","orcid":"","institution":"Private Practice","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Theo","middleName":"","lastName":"Verwey","suffix":""}],"badges":[],"createdAt":"2020-12-06 19:58:23","currentVersionCode":1,"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-123044/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-123044/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":4212316,"identity":"d03a9ca6-f834-4d60-89c9-7b9fe107b2bd","added_by":"auto","created_at":"2020-12-12 00:12:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":65127,"visible":true,"origin":"","legend":"Chest X-Rays Report (23 June 2020): Bilateral patchy and striated groundglass opacity more prominent right lung\nand left lower lobe. Bilateral lower lobe atelectasis.","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/d12ae4a48468082c2b4b873c.png"},{"id":4212317,"identity":"01c1bd03-faa1-412d-962a-b090d8cdb276","added_by":"auto","created_at":"2020-12-12 00:12:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":113875,"visible":true,"origin":"","legend":"Chest X-Rays Report (26 June 2020): Perihilar bronchial cuffing and tram tracking is suggestive of bronchitis. No\ndiscrete consolidation or groundglass opacity to suggest a fulminant Lower respiratory tract infection or COVID-19.","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/e253acc118e4e1f7ce0eba2f.png"},{"id":4212318,"identity":"39ac3962-3fe0-48bf-8765-270e4a628347","added_by":"auto","created_at":"2020-12-12 00:12:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":137368,"visible":true,"origin":"","legend":"Sirtuins and acute inflammation of sepsis: the extreme stress response of sepsis rapidly induces a systemic and\npotentially lethal hyperinflammatory state (red), which shifts within hours to a counterreactive hypoinflammation/adaptation\nphase (blue). NAD+ activation of sirtuins directs this switch. Mechanistically, nuclear SIRT1 levels briefly drop when\nhomeostasis deviation initiates the glycolysis-dependent hyperinflammation, but within hours nuclear and mitochondrial sirtuin\nactivation shifts glycolysis to fatty acid oxidation. This metabolic reprogramming globally represses immunity, affecting\nneutrophils, monocytes, dendritic cells, NK cells, and T lymphocytes. Resolution of acute inflammation and sepsis rebalances\nsirtuins and inflammation to restore homeostasis. Persistent elevation of sirtuins and hypoinflammation as a result lead to death\n(denoted by light blue area).(2)","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/a22c78d38d03679c4b0712a3.png"},{"id":4212319,"identity":"720260a9-c89f-41fc-b3c4-a2a129acb8b2","added_by":"auto","created_at":"2020-12-12 00:12:01","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":88733,"visible":true,"origin":"","legend":"Sirtuins and chronic inflammation: during homeostasis (grey arrow), there are small perturbations in sirtuin levels\nwithout inflammation. During chronic inflammatory states (denoted by pink), persistent decreases in SIRT1 levels/activity\nsustain glycolysis-dependent proinflammatory pathways. This immunometabolic inflexibility alters the bioenergy homeostasis\nset point, which is rebalanced by increasing SIRT1 activity (2)","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/90162f269f4045baa4a8eabb.png"},{"id":4212320,"identity":"c5946121-e081-4c8e-ac4e-959b5658ed56","added_by":"auto","created_at":"2020-12-12 00:12:01","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":115631,"visible":true,"origin":"","legend":"Sirtuins and obesity with sepsis: obesity is associated with low-sirtuin levels/activity, but mechanisms responsible for\nthis imbalance are unknown. If sepsis occurs in obese individuals with low SIRT1, the early hyperinflammatory phase is\naccentuated and counteractive adaptation stage may be prolonged. Activating SIRT1 before obesity-associated sepsis\nprevents the accentuated acute inflammatory reaction. (2)","description":"","filename":"Fig5.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/85b0b6f3f4e66af4751f074f.png"},{"id":4212321,"identity":"c74ff13c-2ca5-48db-896a-c5b041f89793","added_by":"auto","created_at":"2020-12-12 00:12:01","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":143082,"visible":true,"origin":"","legend":"Clinical courses of major symptoms and outcomes and duration of viral shedding from illness onset in patients hospitalised with\nCOVID-19 -","description":"","filename":"Fig6.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/cb5280579448403e60a1c356.png"},{"id":4212322,"identity":"27202f17-ed25-4283-ae31-6d8668f04dfd","added_by":"auto","created_at":"2020-12-12 00:12:02","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":38206,"visible":true,"origin":"","legend":"Graph 1 - NAD+/NADH ratio before and after genuiNAD. The aim is to modulate the adaptation phase of the immune response\nby normalizing the NAD+/NADH ratio to 50/50. NAD+/NADH Before = 87/13 After 44/56","description":"","filename":"Graph1.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/8567d71b5ef6cb8b20208915.png"},{"id":4212323,"identity":"eb9f21ea-26ee-4c64-88d0-8e016f09f6ec","added_by":"auto","created_at":"2020-12-12 00:12:02","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":39110,"visible":true,"origin":"","legend":"Graph 2 - NAD+/NADH ratio before and after pulseNAD. The aim is to modulate the adaptation phase of the immune response\nby normalizing the NAD+/NADH ratio to 50/50. NAD+/NADH Before = 87/13 After 44/56","description":"","filename":"Graph2.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/d111c0acc4ec2f3ad3282289.png"},{"id":4212324,"identity":"9afbdfa6-90d9-41fa-82b8-5c0a97dd06f9","added_by":"auto","created_at":"2020-12-12 00:12:02","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":39197,"visible":true,"origin":"","legend":"Graph 3 - NAD+/NADH ratio before and after diaNAD. The aim is to modulate NAD+/NADH ratio to improve the management of\nDiabetes Mellitus Type 2. NAD+/NADH Before = 56/44 After 78/22.","description":"","filename":"Graph3.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/912a338ee0ec144b58237097.png"},{"id":4212325,"identity":"235bcfb5-6969-4599-9154-36cc82ece418","added_by":"auto","created_at":"2020-12-12 00:12:02","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":32291,"visible":true,"origin":"","legend":"Graph 4 - Resolution of the adaptation / hypoinflammatory phase of the immune response. NAD+/NADH ratio indicates return\nto homeostasis.","description":"","filename":"Graph4.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/d37c16761cd276e9c136da1a.png"},{"id":4212326,"identity":"a2118af1-b031-4c4d-9d61-9039a00f09b7","added_by":"auto","created_at":"2020-12-12 00:12:02","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":43006,"visible":true,"origin":"","legend":"Graph 5 - Lymphocyte % before and during admission","description":"","filename":"Graph5.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/0133455865362e81a1ed78a0.png"},{"id":4212327,"identity":"8776211d-eaff-45f0-af76-6f288e195a24","added_by":"auto","created_at":"2020-12-12 00:12:02","extension":"png","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":49374,"visible":true,"origin":"","legend":"Graph 6 - Normalisation of LDH levels.","description":"","filename":"Graph6.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/2827fd05dc4e7377701cac88.png"},{"id":4212328,"identity":"75d4d2a7-eb03-4613-a900-80fd8a20f288","added_by":"auto","created_at":"2020-12-12 00:12:02","extension":"png","order_by":13,"title":"Figure 13","display":"","copyAsset":false,"role":"figure","size":46219,"visible":true,"origin":"","legend":"Graph 7 - C-Reactive Protein levels decreased indicating decreased inflammation.","description":"","filename":"Graph7.png","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1/fa1602d0c0feee0ffe340796.png"},{"id":13564727,"identity":"b09ba832-68b0-4b8b-b6eb-5366618bc0b1","added_by":"auto","created_at":"2021-09-17 03:22:01","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":949292,"visible":true,"origin":"","legend":"","description":"","filename":"COVID19CaseReport1DMT2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1_covered.pdf"},{"id":4212329,"identity":"23b70bc5-bc53-4839-afbd-6588cc043ce4","added_by":"auto","created_at":"2020-12-12 00:12:11","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":634702,"visible":true,"origin":"","legend":"","description":"","filename":"COVID19CaseReport1DMT2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-123044/v1_stamped.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eCase Report 1: NAD+ Oscillation Therapy (NOT) to treat Covid-19 aggravated by poorly controlled Diabetes Melitus Type 2\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"\u003cp\u003eThis preprint is available for \u003ca href='/article/rs-123044/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eDECLARATION OF CONSENT: We hereby declare that the patient consented to publication of his anonymised clinical data, as well as the patient perspective. Written consent has been obtained.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"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":"NAD+ Oscillation Therapy (NOT), COVID-19, Diabetes Mellitus Type 2, Hypertension, Nicotinamide Adenine Dinucleotide (NAD+), Reduced Nicotinamide Adenine Dinucleotide (NADH)","lastPublishedDoi":"10.21203/rs.3.rs-123044/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-123044/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe report on a case of a 50 year old diabetic, obese and hypertensive male patient that developed severe disease, was admitted and treated with NAD+ Oscillation Therapy (NOT) and then discharged in a stable condition within 5 days (not requiring home oxygen therapy). In addition to the favourable outcome in regards to severe COVID-19 disease, the patient’s blood glucose levels were better controlled after resolution of COVID-19 and the patient has no apparent post-COVID-19 morbidity, which has been reported in countries across the world.\u003c/p\u003e\u003cp\u003eNAD+ Oscillation Therapy is a novel medical treatment developed in South Africa. NAD+ Oscillation Therapy envelops the real time measurement of the NAD+/NADH ratio and modulation of the ratio with the goal of restoration of homeostasis. This supports the primary role of the immune system which is protection and restoration.\u003c/p\u003e\u003cp\u003eThis case shows a favourable treatment outcome in a high risk patient that developed severe disease. Treatment was initiated early and hospitalization was done before laboratory markers reached critical levels. This case highlights the importance of early treatment initiation, effective patient counselling re home care (recognition of sepsis and respiratory distress), NOT as a realtime treatment method of sepsis and the advantage of NOT as a treatment modality in COVID-19 patient care.\u003c/p\u003e","manuscriptTitle":"Case Report 1: NAD+ Oscillation Therapy (NOT) to treat Covid-19 aggravated by poorly controlled Diabetes Melitus Type 2","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-12-12 00:11:59","doi":"10.21203/rs.3.rs-123044/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":"d5fcf9de-05a0-49a1-901b-207465a06978","owner":[],"postedDate":"December 12th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":1352317,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2020-12-12T00:11:59+00:00","versionOfRecord":[],"versionCreatedAt":"2020-12-12 00:11:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-123044","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-123044","identity":"rs-123044","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}