Abstract
The pandemic has supercharged growing awareness of the gut microbiome and the gut-brain-axis as determinants of human health. Zonulin, a circulating protein that increases intestinal and endothelial permeability, has emerged as a central player. This protein can be activated by proteases secreted by Candida, opening the door to myriad autoimmune and other chronic diseases. Many of these are seen in long Covid (LC). Candida hyphal walls express proteins that are analogous to gliadin/gluten (celiac disease antibodies) and that are GPCRs, e.g., Crohn’s disease antibodies present only in eukaryotes that trigger anti-gliadin and anti-GPCR autoantibodies respectively. These two autoantibody producing pathways both activate zonulin and may encompass the broad spectrum of autoimmune diseases seen in LC. The spike protein S on SARS CoV2 can attach to both ACE2 receptor and Toll-like receptor4 (TLR4) bearing cells. The latter can also activate zonulin. A hypothetical pathophysiologic model is proposed implicating Candida overgrowth, aggravated by Covid-19, in not only the genesis of LC but also that of autoimmune disease, dementia, cancer, many chronic diseases, and aging.