COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. In this study, the authors show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. They also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, they observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. The authors concluded underlying that their findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.
Yang L, Kim TW, Han Y, Nair MS, Harschnitz O, Zhu J, Wang P, Koo SY, Lacko LA, Chandar V, Bram Y, Zhang T, Zhang W, He F, Pan C, Wu J, Huang Y, Evans T, van der Valk P, Titulaer MJ, Spoor JKH, Furler O'Brien RL, Bugiani M, D J Van de Berg W, Schwartz RE, Ho DD, Studer L, Chen S. SARS-CoV-2 infection causes dopaminergic neuron senescence. Cell Stem Cell. 2024 Feb 1;31(2):196-211.e6. doi: 10.1016/j.stem.2023.12.012.