Until now after nearly two years from lethally pandemic of covid-19 which is considered a joker virus as bypass many immune defenses in our bodies like innate and adaptive immunity with all types of cells but there are important markers at the long road for treatment like Interleukin (Il-6), neutrophils, high ferritin, high D dimer. Also, post-covid or long covid effects like neuropsychiatric problems like smell dysfunctions and hormonal dysfunctions. Therefore, this article will give a spotlight on the adrenal gland as a place where the immune and endocrine systems meet. Additionally, dexamethasone has no effect on Il-6 secreted from adrenal cortex and this allows Il-6 to be produced during stress. We need a new classification IL-6 at physiological and pathological aspects as the stimulatory factors are different. Endocrine Il-6 is stimulated by ACTH but the immune Il-6 is stimulated by il-1β and angiotensin II. Of note, dexamethasone saves critically covid-19 patients but in the same time has no affection on Il-6 of endocrine origin either basal or stimulated. Therefore, adrenal gland serves as a vital link between the endocrine and immunological systems at the pathogenesis of covid-19. Besides, Il-6 is the key sex-linked variation at their immune responses.