Abnormalities on lung CT and brain MRI have been correlated to functional changes, including dyspnea with air trapping and cognitive deficits, respectively, but they are not sensitive enough to distinguish an inflammatory versus a microthrombotic process. As PASC, like COVID-19, is a systemic process, we hypothesize that a simple 4 mm cutaneous punch biopsy of normal-appearing deltoid skin, a diagnostic method our group has employed for over a decade to investigate thrombotic microangiopathies linked to atypical hemolytic-uremic syndrome and hematopoietic stem cell transplantation and, most recently, acute COVID-19, should permit pathophysiologic explorations of PASC. Direct biopsy of other accessible tissues, including lung and peripheral nerve, could also be pursued. This could enable collection of evidence for vascular damage, microthrombi, and direct SARS-CoV-2 infection. Viral signals in stool and peripheral blood and hematologic/immunologic abnormalities linked to PASC may also be followed longitudinally. It should be recognized that the possible treatments illustrated are based on pathophysiology hypotheses and have not been evaluated in clinical trials. IVIG, intravenous immunoglobulin; sTM, soluble thrombomodulin.