text: A Paradigm for Post Covid 19 Fatigue Syndrome Analogous to ME CFS A significant proportion of COVID 19 patients are suffering from prolonged Post COVID 19 Fatigue Syndrome with characteristics typically found in Myalgic Encephalomyelitis Chronic Fatigue Syndrome ME CFS However no clear pathophysiological explanation as yet has been provided A novel paradigm for a Post COVID 19 Fatigue Syndrome is developed here from a recent unifying model for ME CFS Central to its rationale SARS CoV 2 in common with the triggers viral and non viral of ME CFS is proposed to be a physiologically severe i stressor i which could be targeting a i stress integrator i within the brain the hypothalamic paraventricular nucleus PVN It is proposed that inflammatory mediators released at the site of COVID 19 infection would be transmitted as i stress signals via i humoral and neural pathways which overwhelm this i stress center i In genetically susceptible people an intrinsic i stress threshold i is suggested to be exceeded causing ongoing dysfunction to the hypothalamic PVNs complex neurological circuitry In this compromised state the hypothalamic PVN might then be hyper sensitive to a wide range of lifes ongoing physiological i stressors i This could result in the reported post exertional malaise episodes and more severe relapses in common with ME CFS that perpetuate an ongoing disease state When a certain i stress tolerance level i is exceeded the hypothalamic PVN can become an epicenter for microglia induced activation and neuroinflammation affecting the hypothalamus and its proximal limbic system which would account for the range of reported ME CFS like symptoms A model for Post COVID 19 Fatigue Syndrome is provided to stimulate discussion and critical evaluation Brain scanning studies incorporating increasingly sophisticated imaging technology should enable chronic neuroinflammation to be detected even at a low level in the finite detail required thus helping to test this model while advancing our understanding of Post COVID 19 Fatigue Syndrome pathophysiology 