Fig. 1

The aestivation hypothesis, which is the subject of the present investigation, is that there is a metabolic response to dehydration that induces the production of the organic osmolytes urea and glucose. This requires protein breakdown, which is further hypothesized to cause physical long-COVID because of the muscle weakness. The main parameters investigated in the present study are estimated osmolality (eOSM = 2*Na⁺ + 2*K⁺ + Glucose + Urea) that is used as a measure of dehydration. The degree of aestivation is measure as the decreasing proportion of ionic (sodium and potassium) osmolytes to total osmolality, and increasing proportion of organic osmolytes (glucose and urea). Finally, the metabolic shift to protein breakdown is investigated using plasma metabolomics to detect release of amino acids that will, in turn, be used by the liver for gluconeogenesis and urea synthesis