Heiner Schaal

Severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) is the causative agent of coronavirus disease 2019 (COVID‐19). In less than three years, an estimated 600 million infections with SARS‐CoV‐2 occurred worldwide, resulting in a pandemic with tremendous impact especially on economic and health sectors. Initially considered a respiratory disease, COVID‐19, along with its long‐term sequelae (long‐COVID) rather is a systemic disease. Neurological symptoms like dementia or encephalopathy were reported early during the pandemic as concomitants of the acute phase and as characteristics of long‐COVID. An excessive inflammatory immune response is hypothesized to play a major role in this context. However, direct infection of neural cells may also contribute to the neurological aspects of (long)‐COVID‐19. To mainly explore such direct effects of SARS‐CoV‐2 on the central nervous system, human brain organoids provide a useful platform. Infecting these three‐dimensional tissue cultures allows the study of viral neurotropism as well as of virus‐induced effects on single cells or even the complex cellular network within the organoid. In this review, we summarize the experimental studies that used SARS‐CoV‐2‐infected human brain organoids to unravel the complex nature of (long)‐COVID‐19‐related neurological manifestations.