text: Persistent Brainstem Dysfunction in Long COVID A Hypothesis Long COVID is a postviral illness that can affect survivors of COVID 19 regardless of initial disease severity or age Symptoms of long COVID include fatigue dyspnea gastrointestinal and cardiac problems cognitive impairments myalgia and others While the possible causes of long COVID include long term tissue damage viral persistence and chronic inflammation the review proposes perhaps for the first time that persistent brainstem dysfunction may also be involved This hypothesis can be split into two parts The first is the brainstem tropism and damage in COVID 19 As the brainstem has a relatively high expression of ACE2 receptor compared with other brain regions SARS CoV 2 may exhibit tropism therein Evidence also exists that neuropilin 1 a co receptor of SARS CoV 2 may be expressed in the brainstem Indeed autopsy studies have found SARS CoV 2 RNA and proteins in the brainstem The brainstem is also highly prone to damage from pathological immune or vascular activation which has also been observed in autopsy of COVID 19 cases The second part concerns functions of the brainstem that overlap with symptoms of long COVID The brainstem contains numerous distinct nuclei and subparts that regulate the respiratory cardiovascular gastrointestinal and neurological processes which can be linked to long COVID As neurons do not readily regenerate brainstem dysfunction may be long lasting and thus is long COVID Indeed brainstem dysfunction has been implicated in other similar disorders such as chronic pain and migraine and myalgic encephalomyelitis or chronic fatigue syndrome 