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Elderly patients could be given boosters to make immune systems ‘younger’ and fight coronavirus better: Study

Scientists from Harvard Medical School say the 'most exciting and potentially impactful technologies' to treat COVID-19 are those that activate the body’s defenses against aging
UPDATED MAY 5, 2020
(Getty Images)
(Getty Images)

Older coronavirus patients, who are at high risk, could be given drugs to make their immune systems ‘younger’ and respond better to treatments, suggest researchers from Harvard Medical School, Boston. 

Stating that a person’s immune system is the body’s first line of defense against coronaviruses, the scientists believe that a way of protecting elderly COVID-19 patients is to give them NAD+ boosters, supplements that contain nicotinamide riboside, a form of Vitamin B3. When taken as a supplement, the body converts nicotinamide riboside to NAD+, which stands for nicotinamide adenine dinucleotide, a key compound found in all living beings. With age, the body loses its capacity to make this key element of energy production. 

“Nicotinamide adenine dinucleotide is a molecule responsible for turning nutrients into energy and repairing DNA damage from aging. It is essential for cellular function and metabolism. But NAD+ declines by as much as 50% with age, so prominent anti-aging scientists have been exploring how to stimulate the body's levels in the hope of turning back the tide of age-related decline,” writes an expert in a blog. 

According to researchers of the current study, the most exciting and potentially impactful technologies to treat COVID-19 are those that “activate the body’s defenses against aging.” “It may even be possible to reset the age of cells and tissues so currently high-risk individuals can respond to viral infections as though they were young,” says the researchers in their findings in a pre-print, which is yet to be peer-reviewed. 

The US Centers for Disease Control and Prevention (CDC) says that older adults and people of any age who have serious underlying medical conditions might be at higher risk for severe illness from COVID-19. “Based on what we know now, those at high-risk for severe illness from COVID-19 are people 65 years and older, people who live in a nursing home or long-term care facility, and people of all ages with underlying medical conditions, particularly if not well controlled,” says the CDC. 

The CDC says that older adults and people of any age who have serious underlying medical conditions might be at higher risk for severe illness from COVID-19 (Getty Images)

Disease severity and outcome

The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient’s age. Over 80% of hospitalizations are those over 65 years of age with a greater than 23-fold greater risk of death, says the research team. 

“In the clinic, COVID-19 patients most commonly present with fever, cough, and dyspnea. Particularly in those over 65, it can progress to pneumonia, lung consolidation, cytokine release syndrome, coagulopathy, multiple organ failure, and death. Comorbidities such as cardiovascular disease, diabetes, obesity, and hypertension increase the chances of fatal disease, but they alone do not explain the variability in COVID-19 symptoms,” say experts.

According to the researchers, the ability to control viral load is one of the best prognostics of whether a patient will have mild symptoms or advance to severe COVID-19. For the immune system to effectively suppress then eliminate SARS-CoV-2, it must perform four main tasks:  recognize, alert, destroy, and clear. “Each of these mechanisms is known to be dysfunctional and increasingly heterogeneous in the elderly,” the team explains.

Why NAD+?

According to the researchers, during aging, the immune system changes in two major ways. One is a gradual decline in an immune function called immunosenescence, which hampers “pathogen recognition, alert signaling, and clearance.” “The other classic immune system change is a chronic increase in systemic inflammation called inflammaging, which arises from an overactive yet ineffective alert system,” says the team.

Accordingly, the researchers discussed treatments in the study that could increase survival in the elderly, not simply by inhibiting the virus, but by restoring patients’ ability to clear the infection.

Scientists have made a lot of progress in understanding how aging works on the cellular level. And an important thing they have discovered has to do with a molecule called nicotinamide adenine dinucleotide. It is a coenzyme found in all living cells and performs critical jobs in the human body. “NAD+, or nicotinamide adenine dinucleotide, is a critical coenzyme found in every cell in your body, and it’s involved in hundreds of metabolic processes.

But NAD+ levels decline with age. NAD+ has two general sets of reactions in the human body: helping turn nutrients into energy as a key player in metabolism and working as a helper molecule for proteins that regulate other cellular functions. These processes are incredibly important,” according to an article.

During aging, the amount of the chemical compound NAD+ in the body declines, which could be a “major contributor” to the aggressive effects of the coronavirus on the elderly, the study claims.

During aging, the amount of the compound NAD+ in the body declines, which could be a 'major contributor' to the aggressive effects of the coronavirus on the elderly, say experts (Getty Images)

When NAD+ levels drop, it might promote hyperactivation of NLRP3 (responsible for the activation of inflammatory responses) and trigger cytokine storms in COVID-19 patients, where the body starts to attack its own cells and tissues rather than just fighting off the virus. By giving NAD+ boosters to elderly patients, their immune systems could be in a better position to fight COVID-19 and respond better to treatment, suggests the team. 

“One in two fatal cases of COVID-19 experience a cytokine storm, 82% of whom are over the age of 60. Though there may be many simultaneous triggers of the storm, abundant evidence indicates that inflammaging is a major driver, exacerbated by obesity, poor diets and oral health, and sedentary lifestyles,” they explain.

The team suggests that maintaining NAD+ levels may, therefore, alleviate COVID-19 symptoms “Given the increasing evidence that lower NAD+ levels in the lung and vascular endothelium contribute to poor COVID-19 outcomes, NAD boosters, such as the NAD+ precursors NMN and NR, have been suggested as first-line treatments against COVID-19, especially aged patients,” says the study. 

The researchers further say that in the aged, immune responses to vaccination are often weak or defective. “Therefore, in designing vaccines against SARS-CoV-2, it will be important to consider that older people may not respond as well to vaccines as young people,” the team recommends. They emphasize that studies that follow the long-term consequences of SARS-CoV-2 (the virus that causes COVID-19) infection in older people will also be critical to understand the long-term health consequences of the novel coronavirus. 

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