Understanding the neurological implications of acute and long COVID using brain organoids

Abstract

As early as in the acute phase of the coronavirus disease 2019 (COVID-19) pandemic, the research community voiced concerns about the long-term implications of infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like many other viruses, can trigger chronic disorders that last months or even years. Long COVID, the chronic and persistent disorder lasting more than 12 weeks after the primary infection with SARS-CoV-2, involves a variable number of neurological manifestations, ranging from mild to severe and even fatal. In vitro and in vivo modeling suggest that SARS-CoV-2 infection drives changes within neurons, glia and the brain vasculature. In this Review, we summarize the current understanding of the neuropathology of acute and long COVID, with particular emphasis on the knowledge derived from brain organoid models. We highlight the advantages and main limitations of brain organoids, leveraging their human-derived origin, their similarity in cellular and tissue architecture to human tissues, and their potential to decipher the pathophysiology of long COVID.

Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice

“…Symptoms of PCS include fatigue, impaired breathing (Tsuchida et al, 2023), arthralgia and myalgia (Romero et al, 2023), bone pain (Davis et al, 2021), cardiac symptoms as palpitations (Jiang et al, 2021), gastrointestinal changes including altered bowel habits and bloating (Comelli et al, 2022), as well as neuropsychiatric impairment, such as cognitive complaints (often referred to as “brain fog”), anxiety and depression (reviewed in Badenoch et al, 2022). These neuropsychiatric sequelae constitute a major concern since they may be associated with an increased risk of developing long-term cognitive impairment and dementia (García-González et al, 2023). A systematic review and meta-analysis examining persistent neuropsychiatric symptoms following COVID-19 revealed that among nearly 19,000 patients, 27.4% reported sleep disorder, 24.4% experienced fatigue, and 15.7% exhibited symptoms consistent with post-traumatic stress disorder (PTSD) (Simani et al, 2021), 35,5% cognitive dysfunction, 19.1% anxiety, 12.9% depression, 11.4% dysosmia, 7.4% dysgeusia, 6.6% headache, 5.5% disorder sensorimotor and 2.9% dizziness (Badenoch et al, 2022).…”