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U.S.A."],"published-print":{"date-parts":[[2022,11,15]]},"abstract":"<jats:p>The COVID-19 pandemic has created a large population of patients who are slow to recover consciousness following mechanical ventilation and sedation in the intensive care unit. Few clinical scenarios are comparable. Possible exceptions are the rare patients in post-cardiac arrest coma with minimal to no structural brain injuries who recovered cognitive and motor functions after prolonged delays. A common electroencephalogram (EEG) signature seen in these patients is burst suppression [8]. Biophysical modeling has shown that burst suppression is likely a signature of a neurometabolic state that preserves basic cellular function \u201cduring states of lowered energy availability.\u201d These states likely act as a brain protective mechanism [9]. Similar EEG patterns are observed in the anoxia resistant painted turtle [24]. We present a conceptual analysis to interpret the brain state of COVID-19 patients suffering prolonged recovery of consciousness. We begin with the Ching model and integrate findings from other clinical scenarios and studies of the anoxia-tolerant physiology of the painted turtle. We postulate that prolonged recovery of consciousness in COVID-19 patients could reflect the effects of modest hypoxic injury to neurons and the unmasking of latent neuroprotective mechanisms in the human brain. This putative protective down-regulated state appears similar to that observed in the painted turtle and suggests new approaches to enhancing coma recovery [12].<\/jats:p>","DOI":"10.1073\/pnas.2120221119","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T15:17:01Z","timestamp":1667834221000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":13,"title":["Protective down-regulated states in the human brain: A possible lesson from COVID-19"],"prefix":"10.1073","volume":"119","author":[{"given":"Nicholas D.","family":"Schiff","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Feil Family Brain Mind Research Institute, Weill Cornell Medicine, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emery N.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Institute for Medical Engineering and Science and Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,11,7]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2009575"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-020-01133-9"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0808281"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002334"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25838"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011355"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26342"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25690"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121461109"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.582794"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16667"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2004.03.013"},{"key":"e_1_3_4_13_2","first-page":"90","article-title":"Constitutive preconditioning: The anoxia tolerant freshwater turtle as a model organism of the preconditioned phenotype","volume":"2","author":"Milton S.","year":"2019","unstructured":"S. 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