Most people with COVID infection feel better within a few days or weeks of their first symptoms and fully recover within 12 weeks. For some people, symptoms can last longer and when it does, it is called long COVID syndrome. Symptoms commonly associated with long COVID include fatigue, joint or muscle pain, shortness of breath, changes in smell or taste, persistent rashes, hair loss, an irregular heart rate, dizziness upon standing up, unusual changes in menstrual cycles, depression and difficulty thinking or concentrating (brain fog). The World Health Organization (WHO) definition of long COVID requires symptoms to be present 3 months from the onset of COVID, last for at least 2 months, and those symptoms cannot be explained by an alternative diagnosis.¹ In a recent study, using a very conservative estimation method, approximately 6% of individuals who had symptomatic COVID infection had continued symptoms 3 months later. Long COVID symptoms were more common in women and lasted for an average of 9 months, but were still present in some individuals for at least 12 months.² Other studies have indicated that as many as 87% report persistence of at least 1 symptom, particularly fatigue and shortness of breath.³

Nicotinamide adenine dinucleotide (NAD) is a cofactor (a substance whose presence is essential for activity) for a number of cellular processes including energy production, DNA repair, gene expression, antioxidant activity, brain dopamine production, and immunological functions.⁴ Because of its role in DNA repair and gene expression, it may play a pivotal role in extending the life of the cell and therefore, slowing the aging process.⁵ NAD can exist in two forms: NAD+ and NADH (also referred to as the reduced form of NAD). In the context of energy metabolism, NAD+ and NADH are the same molecule, NADH is simply the electron-carrying form of NAD+. Recently, COVID infection has been shown to strongly increase the activity of several genes with the potential to consume NAD+ and dramatically deplete cellular NAD+ levels.⁶ NAD is therefore an emerging regulator of immune responses during viral infections, and may be a promising therapeutic target for coronavirus disease.⁷

Long COVID could be described as a virally induced chronic and self-perpetuating state where inflammation is continuous and unresolved.⁸ Despite our limited understanding of how COVID infection promotes this persistent disease state, mitochondrial (organelle within the cell where energy production occurs) dysfunction has been recognized as a contributing factor to acute COVID infection and, more recently, to the development of long COVID. There is now adequate evidence that disruption in NAD supply and use resulting in mitochondrial dysfunction (decreased energy production) following COVID infection is key to the development of long COVID.⁹ Thus, supplementation with NAD may accelerate recovery from long COVID. The most straightforward way to raise NAD concentrations is to provide additional precursors to boost NAD production. It should be noted that NAD+ cannot be taken up directly by the cell, but its precursors such as the NADH found in NutraHeal Plus are a good option to replenish supply. In one study of approximately 300 patients with COVID, the use of a NAD precursor (in combination with a few amino acids) reduced the time to complete recovery from 9.2 to 5.7 days.¹⁰ With the animal and human data now pointing to a key role of NAD depletion in the development of long COVID, multiple clinical trials of NAD+ boosters are underway.⁷

1. Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV, Condition WHOCCDWGoP-C-. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. Apr 2022;22(4):e102-e107. doi:10.1016/S1473-3099(21)00703-9
2. Global Burden of Disease Long CC, Wulf Hanson S, Abbafati C, et al. Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021. JAMA. Oct 25 2022;328(16):1604-1615. doi:10.1001/jama.2022.18931
3. Carfi A, Bernabei R, Landi F, Gemelli Against C-P-ACSG. Persistent Symptoms in Patients After Acute COVID-19. JAMA. Aug 11 2020;324(6):603-605. doi:10.1001/jama.2020.12603
4. Braidy N, Berg J, Clement J, et al. Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes. Antioxid Redox Signal. Jan 10 2019;30(2):251-294. doi:10.1089/ars.2017.7269
5. Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Exp Gerontol. Apr 2020;132:110831. doi:10.1016/j.exger.2020.110831
6. Heer CD, Sanderson DJ, Voth LS, et al. Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity. J Biol Chem. Dec 25 2020;295(52):17986-17996. doi:10.1074/jbc.RA120.015138
7. Zheng M, Schultz MB, Sinclair DA. NAD(+) in COVID-19 and viral infections. Trends Immunol. Apr 2022;43(4):283-295. doi:10.1016/j.it.2022.02.001
8. Nunn AVW, Guy GW, Brysch W, Bell JD. Understanding Long COVID; Mitochondrial Health and Adaptation-Old Pathways, New Problems. Biomedicines. Dec 2 2022;10(12)doi:10.3390/biomedicines10123113
9. Block T, Kuo J. Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome. Clin Pathol. Jan-Dec 2022;15:2632010X221106986. doi:10.1177/2632010X221106986
10. Altay O, Arif M, Li X, et al. Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19. Adv Sci (Weinh). Sep 2021;8(17):e2101222. doi:10.1002/advs.202101222