Understanding the immune response in COVID-19 – new opportunities and new insights

Professor Guy Richards - Charlotte Maxeke Academic Hospital, Johannesburg

Published in: deNovo Medica, July 2021 © 2021 deNovo Medica
This article describes:

  • The fundamental role of nicotinamide adenine dinucleotide (NAD+) in multiple metabolic pathways and its critical role in immune function
  • NAD+ biosynthesis and the use of supplements to enhance cellular NAD+ levels
  • What is known about the interplay between the immune system and SARS-CoV-2.


  • …NAD+ levels decline with age and are also reduced in conditions associated with oxidative stress as occurs with hypertension, diabetes and obesity, all of which have been observed to have higher mortality following infection with SARS-CoV-2.” (bold added)
  • “…New insights regarding the metabolic abnormalities and hyperinflammatory response that are associated with COVID-19 suggest that a deficiency in nicotinamide adenine dinucleotide (NAD+), unmasked by a significant increase in oxidative stress, may be a primary factor related to the disease spectrum and the risk for mortality (bold added)
  • “…Nutritional support to restore levels of NAD+ and associated enzymes could minimise disease severity if administered prophylactically and/or therapeutically. The significance of this, if proven, has far-reaching consequences in the management of COVID-19 especially in third world countries, where resources and finances are limited…” (bold added)
  • “ …A recent phase II clinical study has found that the combination of a nutritional cocktail that included NR [Nicotinamide Riboside] together with the standard of care reduced recovery time by nearly 30% compared to standard of care alone (6.6 vs 9.3 days) in 304 patients with mild to moderate COVID-19…” (bold added)
  • “…The cell has innate processes which serve as a first line of defence against virally mediated damage. These defence mechanisms consume and deplete NAD+ and in so doing, intracellular immune defences may be compromised.”
  • “If there is insufficient NAD+ available then the SIRTs [Sirtuins]are unable to suppress viral replication or the inflammatory response.”
  • Insufficient NAD+ would lead to viral persistence and SIRT [Sirtuins]inhibition without modulation of the production of proinflammatory cytokines, which contribute to hyperinflammation and the cytokine storm (bold added)
  • “...NAD+ has a vital role in controlling the ongoing inflammatory state, overactivation of the immune system, and even the cytokine storm.” (emphasis added)
  • “Evidence exists to suggest that COVID-19 interacts with host NAD+ metabolism. In host-pathogen interactions, NAD+ depletion and/or the co-opting of NAD+ generating pathways have been shown to be common mechanisms compromising host-cell defences.” (bold added)
  • Those at higher risk of developing more serious COVID-19 disease may have a deficiency of NAD+, which declines with age and is also reduced in conditions associated with oxidative stress.” (bold added)
  • NAD+ is involved in multiple metabolic pathways including energy metabolism and has several roles in immunological function (bold added)
  • “Cellular NAD+ levels may be enhanced by the use of NAM [Nicotinamide], NR [Nicotinamide riboside] or NA [Nicotinic Acid] supplements (bold added)

Understanding the immune response

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