Can NAD+ Be Used to Aid with COVID-19 and Long COVID?
Severe infection with the SARS-CoV2-2 virus in COVID-19 patients has been consistently linked to a dysregulation of the body’s immune system.1 As the immune response becomes more and more unbalanced, the inflammation triggered by this response begins to cause cell death and tissue damage.
The resulting damage to multiple organs such as the lungs, heart, and brain accounts for common symptoms of COVID-19, which include fatigue, shortness of breath, and chest pain.2,3 Beyond the initial infection, these symptoms can persist in patients for months after they leave the hospital, causing so-called “long COVID". [4]
Crucially, there is a strong link between the severity of the initial SARS-CoV-2 infection and the likelihood of developing long COVID—while only 10% of non-hospitalized patients go on to develop long COVID, in hospitalized patients, this figure reaches 90%.2 Therefore, it is essential to find treatments that can reduce the severity of COVID-19 symptoms during the initial infection.
To understand potential treatments, it is important to look at how the symptoms of COVID-19 emerge at the molecular and cellular levels.
Infection with SARS-CoV-2 causes an overactivation of a specific subtype of immune cells known as “effector T-cells”.5 These cells are responsible for producing cytokines and chemokines—chemical signals that modulate the immune response and induce inflammation.
As effector T-cells become abnormally active in response to SARS-CoV-2, a proinflammatory environment develops in the body, inducing tissue damage.5 In very severe cases, a “cytokine storm” can develop, which can lead to life-threatening systemic inflammation.
Overactivation of a protein in the cell nucleus called PARP-1 forms a key link between SARS-CoV-2 infection and tissue damage. [6]
PARP-1 plays a central role in antiviral defenses in combination with nicotinamide adenine dinucleotide (NAD+), a natural “helper molecule” (coenzyme) that supports healthy metabolism and energy production. PARP-1 breaks down NAD+ into nicotinamide and ADP-ribose, using the ADP-ribose to “tag” and inactivate the SARS-CoV-2 viral genome in the cell nucleus, preventing the virus from replicating. [6]
However, SARS-CoV-2 is able to avoid this antiviral defense by removing the ADP-ribose tag, enabling it to continue replicating.7 As the virus continues to spread, PARP-1 remains overactive for a prolonged period, forcing the cell to use its energy stores of ATP to continually regenerate the nuclear pool of NAD+. Eventually the ATP and NAD+ supplies are depleted, leading to cell death and tissue damage.
Effective medication is necessary to prevent tissue damage during inflammation in COVID-19 and reduce the risk of developing long COVID8—could NAD+ supplements help?
Research suggests that NAD+ administration could provide a potential therapy for COVID-19. By replacing NAD+ consumed by PARP-1 during SARS-CoV-2 infection, supplements could help to prevent the cell from depleting its pool of NAD+, thereby preventing cell death. [6]
In addition, studies suggest that NAD+ can indirectly inhibit PARP-1, preventing runaway inflammation and tissue damage. [6]
Finally, NAD+ acts via multiple molecular pathways to regulate the immune response and the differentiation of T-cells into different subtypes, which might help to rebalance the immune system during SARS-CoV-2 infection. [8]
The NAD+ sublingual lozenges and transdermal patches offered by the Longevity Collective help to supplement natural levels of NAD+ in the body. The research summarized above suggests that by restoring supplies of NAD+ in the body, these supplements may help to rebalance the immune system and treat the symptoms COVID-19 before it develops into long COVID.
Disclaimer: NAD+ products have not been evaluated by the FDA for COVID recovery and more research needs to be done.
