Neuroimmune pathophysiology of long COVID

Although COVID-19 was originally considered a respiratory illness, it is now well established that SARS-CoV-2 infection can have far-reaching impacts on the nervous system. Neurological symptoms such as chemosensory dysfunction are frequently observed during acute infection and approximately 10% of COVID-19 cases will go on to develop new or persistent long-term symptoms, a condition known in the literature as post-acute symptoms of COVID-19 (PASC) or by the patient-coined term Long COVID. Common neurological symptoms in Long COVID include new onset cognitive difficulties, dysautonomia, fatigue, and peripheral neuropathy. The emergence of Long COVID has prompted renewed interest in the study of post-acute infection syndromes (PAIS), particularly in the area of neuroimmune interactions. In this review we provide a comprehensive overview of the current body of literature on neurological manifestations of SARS-CoV-2 infection and Long COVID, with an emphasis on neuroimmune mechanisms drawn largely from autopsy studies and animal models. A more complete understanding of neuroimmune crosstalk in Long COVID will not only guide the development of therapies for this highly disabling condition but will also contribute to our general understanding of neuroimmune interactions in health and disease.