Can NAD+ Help with Long COVID Recovery? What We Know

Key Takeaways:

• Long COVID affects millions worldwide, with symptoms that may be linked to immune stress caused by viral infections like COVID-19.

• NAD+ is essential for immune regulation, DNA repair, and cellular energy—functions that can be impaired after viral infections, which may contribute to long COVID symptoms like fatigue and brain fog.

• A new clinical study revealed that supplementation with nicotinamide riboside (NR), an NAD+ precursor, increased NAD+ levels and improved outcomes such as executive function, sleep quality, mood, and fatigue in long COVID patients.

• While initial findings are promising, larger and more rigorous human trials are needed to confirm the effectiveness of boosting NAD+ as a therapeutic option for long COVID recovery.

COVID-19 may have faded from daily headlines, but for millions of people worldwide, the struggle continues for months—or years—after their first positive PCR test. 

More than 778 million COVID-19 cases have been recorded worldwide—and counting. But for many, recovery isn’t as simple as a week of rest and downtime. About 15% still experience lingering symptoms a full year later—a condition now widely known as long COVID, typically diagnosed when fatigue, brain fog, shortness of breath, or other symptoms persist for at least three months after infection.

With long COVID sufferers continuing their advocacy for recognition and treatment, and recent US Senate hearings bringing greater attention to the issue, public awareness is rising—and, with it, a pressing demand to find effective therapies.

With symptoms ranging from brain fog and dizziness to loss of taste and heart palpitations, long COVID can impact nearly every organ system. Because these symptoms can severely diminish quality of life, patients are desperately seeking relief—and one promising approach, highlighted in a recently published study, might be boosting NAD+. 

Newly Published Research Results: Can Boosting NAD+ Help Mitigate Long COVID Symptoms?

Given the growing need for effective treatments for long COVID, a recently published study explored the potential of NAD+ supplementation to alleviate symptoms in affected individuals.

The study, which began in 2021, assessed whether supplementing with a patented form of nicotinamide riboside (NR), a precursor to NAD+, could improve recovery from long COVID symptoms. The NR was supplied by Niagen Bioscience, Inc. for research purposes. 

Researchers evaluated a range of outcomes, including cognitive, neuropsychiatric, physical, functional, and biomarker measures.

This randomized, double-blind, placebo-controlled, parallel-group study involved 58 non-hospitalized participants. Sixty percent received 2,000 mg of Niagen daily for 20 weeks, while the remaining 40% took a placebo for 10 weeks before crossing over to NR supplementation for the final 10 weeks.

The study enrolled people who met the following criteria:

• Documented SARS-CoV-2 infection confirmed by PCR at least two months before joining the study, but not currently infected 

• Persistent cognitive difficulties (“brain fog”) beginning around the time of infection

• At least two ongoing neurological or physical symptoms since COVID-19 infection, such as fatigue, weakness, headache, loss of smell, tingling or numbness, shortness of breath, loss of appetite, heart palpitations or tachycardia, hair loss, musculoskeletal pain, or chest pain

• Not pregnant or lactating

A key finding from this trial was that NR supplementation effectively increased whole blood NAD+ levels and was associated with improvements in participants’ executive functioning, sleep quality, and self-reported fatigue and mood compared to their own baselines.

However, no significant differences were found between the NR and placebo groups in cognitive outcomes measured by various tests, including assessments of real-world thinking, memory, learning, and mental flexibility.

Notably, there were no significant differences in adverse effects between the NR and placebo groups. Additionally, symptom improvement appeared similar whether participants took NR for 10, 15, or 20 weeks, suggesting that 10 weeks of supplementation was sufficient to observe benefits.

Overall, these initial results are promising and position NR supplementation as a potential therapeutic strategy to improve certain symptoms and quality of life in people affected by long COVID. As this study is newly published, it lays important groundwork for ongoing research and conversation around NR supplementation’s role in managing long COVID.

That said, larger trials are still needed to confirm these benefits and clarify which symptoms and systems are most impacted.

NAD+ and Its Role in Immune Health: How This Molecule May Help Fight Long COVID

Understanding NR’s potential role in long COVID first requires exploring how NAD+ plays a role in immune and cellular health.

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme essential for over 500 enzymatic reactions,¹ including those that regulate energy production, DNA repair, and immune cell function—processes often disrupted in COVID-19² and long COVID.

Notably, NAD+ supports enzymes like sirtuins and poly(ADP-ribose) polymerases (PARPs), which support mitochondrial health and help control inflammation during antiviral responses.

NAD+ supports enzymes that both activate and regulate immune responses,² helping the immune system avoid being underactive—allowing infections to spread—or overactive, which can cause damaging inflammation. 

This “Goldilocks zone” means immune responses are strong enough to fight infection but not so strong that they trigger lasting inflammatory states—such as the harmful “cytokine storm” seen in severe COVID-19 cases.³

Maintaining this delicate balance is key to fighting infection without leaving lingering symptoms—and this balance relies heavily on adequate NAD+ levels. Now, let’s explore studies that look at NAD+ precursors—especially nicotinamide riboside (NR)—and their potential to restore NAD+ levels and improve outcomes from viral infections. 

Current Landscape of NAD+ and NR Research on COVID & Long COVID

During infection, like with viruses such as SARS-CoV-2, HIV, and herpes simplex virus (HSV-1), cellular NAD+ pools can drop significantly, as seen in several preclinical models.

For example, an in vitro (cell culture-based) study found that HSV-1 infection reduced NAD+ by up to 80% in some cell types.⁴ This NAD+ depletion may impair DNA repair capacity and dysregulate inflammation, processes implicated in the lingering symptoms of long COVID.

In primary immune cells infected with SARS-CoV-2, NAD+ levels dropped more than threefold, while supplementation with NR reduced viral replication by 2.7-fold.⁵ Similarly, mouse fibroblast cells infected with hepatitis virus experienced a 6.4-fold decrease in viral replication after NR treatment.

Building on these findings, a Phase 3 clinical trial tested a combination of NR, NAC, L-serine, and L-carnitine (combined with the standard treatment of hydroxychloroquine and favipiravir) in patients with mild-to-moderate COVID-19.⁶ This protocol shortened recovery time by 3.5 days compared with placebo, though the design does not allow for conclusions about NR’s contribution alone. 

Another human study examined the effects of nicotinamide (NAM), another NAD+ precursor, on COVID-19 recovery, looking at physical performance, gut microbiome composition, and NAD+ biosynthesis.⁷ 

After six months, participants taking NAM showed significant improvements in recovery, post-COVID syndrome scores, gut microbiome health, and NAD+ production. These findings align with previous research demonstrating NAD+ depletion during viral infections and the benefits of boosting NAD+ levels.

Taken together, these studies suggest that restoring NAD+ during and after infection may help sustain cellular resilience, suppress viral replication, and balance immune responses, making NR a promising candidate for further COVID-19 and long COVID research. 

Currently, three additional clinical trials are underway to explore NAD+ metabolism in the context of COVID-19 and long COVID: investigating NR’s effects in elderly SARS-CoV-2 patients, its impact on mental health post-COVID, and its potential benefits in hospitalized COVID-19 patients with acute kidney injury.

Boosting NAD+ May Help Manage Long COVID Symptoms

NAD+ plays a crucial role in cellular energy production—and no organ uses energy as much as the brain. Our brains are metabolic powerhouses, constantly needing a steady energy supply to function properly.

Two of the most common—and often debilitating—symptoms of long COVID are brain fog and fatigue, which can be hard to quantify but seriously impact quality of life.

Because immune stressors like viruses can drastically deplete NAD+ levels, replenishing it with precursors like NR might better equip the body to fight fatigue and support brain health disrupted by long COVID. Beyond energy production, NAD+ also supports cellular defense and repair mechanisms critical to immune health and recovery.

Although far from peer-reviewed data, anecdotal reports from online communities like Reddit and COVID-19 Long Haulers Support highlight improvements in fatigue, mood, and sleep with NAD+ boosting strategies, underscoring the potential real-world benefits for long COVID sufferers.

Conclusion: Why Boosting NAD+ Has Potential for Long COVID

Long COVID continues to affect millions, months, or even years after the initial infection has faded. Though symptoms can impact multiple organ systems, they are closely linked to immune stress and NAD+ depletion caused by viral infections.

This newly published study on NR supplementation offers promising insights that could shift treatment approaches by targeting these underlying biological mechanisms.

While long COVID remains under-addressed and lacks a definitive cure, growing political support and persistent advocacy from sufferers are opening the door to new, accessible solutions like boosting NAD+ through precursors such as NR.

That said, although NAD+ precursors offer real promise and hope for millions affected by long COVID, larger, more rigorous clinical trials are essential to fully confirm their benefits. 

Please note: The information provided in this blog is for informational purposes only and is not intended to diagnose, treat, cure, mitigate, or prevent any disease.

1. Rajman, L., Chwalek, K., & Sinclair, D. A. (2018). Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metabolism, 27(3), 529–547. https://doi.org/10.1016/j.cmet.2018.02.011
2. Zheng, M., Schultz, M. B., & Sinclair, D. A. (2022). NAD+ in COVID-19 and viral infections. Trends in Immunology, 43(4), 283–295. https://doi.org/10.1016/j.it.2022.02.001
3. Zanza, C., Romenskaya, T., Manetti, A. C., Franceschi, F., Russa, R. L., Bertozzi, G., Maiese, A., Savioli, G., Volonnino, G., & Longhitano, Y. (2022). Cytokine Storm in COVID-19: Immunopathogenesis and Therapy. Medicina, 58(2), 144. https://doi.org/10.3390/medicina58020144
4. Grady, S. L., Hwang, J., Vastag, L., Rabinowitz, J. D., & Shenk, T. (2012). Herpes Simplex Virus 1 Infection Activates Poly(ADP-Ribose) Polymerase and Triggers the Degradation of Poly(ADP-Ribose) Glycohydrolase. Journal of Virology, 86(15), 8259–8268. https://doi.org/10.1128/jvi.00495-12
5. Heer, C. D., Sanderson, D. J., Voth, L. S., Alhammad, Y. M. O., Schmidt, M. S., Trammell, S. A. J., Perlman, S., Cohen, M. S., Fehr, A. R., & Brenner, C. (2020). Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity. Journal of Biological Chemistry, 295(52), 17986–17996. https://doi.org/10.1074/jbc.ra120.015138
6. Altay, O., Arif, M., Li, X., Yang, H., Aydın, M., Alkurt, G., Kim, W., Akyol, D., Zhang, C., Dinler‐Doganay, G., Turkez, H., Shoaie, S., Nielsen, J., Borén, J., Olmuscelik, O., Doganay, L., Uhlén, M., & Mardinoglu, A. (2021). Combined Metabolic Activators Accelerates Recovery in Mild‐to‐Moderate COVID‐19. Advanced Science, 8(17), 2101222. https://doi.org/10.1002/advs.202101222
7. Schreiber, S., Waetzig, G. H., López-Agudelo, V. A., Geisler, C., Schlicht, K., Franzenburg, S., Giuseppe, R. di, Pape, D., Bahmer, T., Krawczak, M., Kokott, E., Penninger, J. M., Harzer, O., Kramer, J., Schrenck, T. von, Sommer, F., Zacharias, H. U., Schreiber, S., Waetzig, G. H., … Rosenstiel, P. (2025). Nicotinamide modulates gut microbial metabolic potential and accelerates recovery in mild-to-moderate COVID-19. Nature Metabolism, 7(6), 1136–1149. https://doi.org/10.1038/s42255-025-01290-1