Furthermore, another signal associated with relentless platelet activation in COVID-19, the prototype alarmin/DAMP HMGB1 promotes neuroinflammation, acting on microglia via the HMGB1/STAT3/p65 axis and autophagy31,32 while causing fatigue in patients with inflammatory bowel disease alone or by amplifying pathways associated with the IL-1 beta response33. This evidence concerns the gene HMGB1 and inflammatory bowel disease.