What I Found in My Clients' Tests After Long COVID — And Why It Changes Everything — Finding #3: CD38, Sirtuin, and the NAD⁺ Collapse — This Is the Core

This is the part I want you to understand most, because it explains why long COVID doesn&#8217;t get better on its own. When LPS enters the bloodstream and inflammation goes chronic, it triggers the upregulation of an enzyme called CD38 . Think of CD38 as a pac-man for a molecule called NAD&#8314; (nicotinamide adenine dinucleotide). NAD&#8314; is not just an energy carrier &#8212; it is the master regulator of cellular health. It is the fuel that powers a family of proteins called sirtuins (specifically SIRT1 and SIRT3), which control mitochondrial function, DNA repair, inflammatory regulation, and the epigenetic programs that determine which genes are switched on or off. When CD38 gets activated by chronic LPS-driven inflammation, it consumes NAD&#8314; faster than the cell can make it. And when NAD&#8314; drops, the sirtuins go quiet. Here is what happens when SIRT1 and SIRT3 lose their NAD&#8314; fuel: SIRT1 normally puts a brake on NF-&#954;B &#8212; the master inflammation switch inside the cell. Without SIRT1 activity, NF-&#954;B stays switched on, producing more inflammatory signals, which produce more CD38, which depletes more NAD&#8314;. A loop that feeds itself. SIRT3 normally maintains the function of the mitochondrial electron transport chain &#8212; the machinery that generates ATP. Without SIRT3, these complexes deteriorate. Energy production collapses further. A