{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T02:15:11Z","timestamp":1784945711710,"version":"3.55.0"},"reference-count":137,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Foundation of the Finnish Otolaryngological Association"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Most SARS CoV-2 infections probably occur unnoticed or cause only cause a mild common cold that does not require medical intervention. A significant proportion of more severe cases is characterized by early neurological symptoms such as headache, fatigue, and impaired consciousness, including respiratory distress. These symptoms suggest hypoxia, specifically affecting the brain. The condition is best explained by primary replication of the virus in the nasal respiratory and\/or the olfactory epithelia, followed by an invasion of the virus into the central nervous system, including the respiratory centers, either along a transneural route, through disruption of the blood-brain barrier, or both. In patients, presenting with early dyspnea, the primary goal of therapy should be the reversal of brain hypoxia as efficiently as possible. The first approach should be intermittent treatment with 100% oxygen using a tight oronasal mask or a hood. If this does not help within a few hours, an enclosure is needed to increase the ambient pressure. This management approach is well established in the hypoxia-related diseases in diving and aerospace medicine and preserves the patient\u2019s spontaneous breathing. Preliminary research evidence indicates that even a small elevation of the ambient pressure might be lifesaving. Other neurological symptoms, presenting particularly in long COVID-19, suggest imbalance of the autonomous nervous system, i.e., dysautonomia. These patients could benefit from vagal nerve stimulation.<\/jats:p>","DOI":"10.3390\/life12050754","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T12:25:57Z","timestamp":1652963157000},"page":"754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prevention and Treatment of Life-Threatening COVID-19 May Be Possible with Oxygen Treatment"],"prefix":"10.3390","volume":"12","author":[{"given":"Jukka","family":"Ylikoski","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland"},{"name":"Helsinki Ear Institute, 00420 Helsinki, Finland"},{"name":"Salustim Group Inc., 90440 Kempele, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarmo","family":"Lehtim\u00e4ki","sequence":"additional","affiliation":[{"name":"Helsinki Ear Institute, 00420 Helsinki, Finland"},{"name":"Salustim Group Inc., 90440 Kempele, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rauno","family":"P\u00e4\u00e4kk\u00f6nen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"M\u00e4kitie","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nrmicro2147","article-title":"Coronaviruses post-SARS: Update on replication and pathogenesis","volume":"7","author":"Perlman","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00281-017-0629-x","article-title":"Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology","volume":"39","author":"Channappanavar","year":"2017","journal-title":"Semin. Immunopathol."},{"key":"ref_3","first-page":"11","article-title":"The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak\u2014An update on the status","volume":"7","author":"Guo","year":"2020","journal-title":"Mil. Med. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s10072-020-04964-8","article-title":"Neurological manifestations of coronavirus disease 2019: Exploring past to understand present","volume":"42","author":"Desai","year":"2021","journal-title":"Neurol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1001\/jamaneurol.2020.1127","article-title":"Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China","volume":"77","author":"Mao","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"116884","DOI":"10.1016\/j.jns.2020.116884","article-title":"WFN Environmental Neurology Specialty Group The neurology of COVID-19 revisited: A proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries","volume":"414","author":"Roman","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1080\/00016489.2020.1773533","article-title":"Pathophysiology of the COVID-19\u2014Entry to the CNS through the nose","volume":"140","author":"Ylikoski","year":"2020","journal-title":"Acta Oto-Laryngol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/jmv.25728","article-title":"The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients","volume":"92","author":"Li","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.cell.2015.03.022","article-title":"Vagal sensory neuron subtypes that differentially control breathing","volume":"161","author":"Chang","year":"2015","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"116824","DOI":"10.1016\/j.jns.2020.116824","article-title":"Neurotropism of SARS-CoV-2: Mechanisms and manifestations","volume":"412","author":"Cardona","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s12035-020-02152-5","article-title":"Multiple Neuroinvasive Pathways in COVID-19","volume":"58","author":"Bougakov","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1021\/acschemneuro.0c00217","article-title":"Is the collapse of the respiratory center in the brain responsible for respiratory breakdown in COVID-19 patients?","volume":"11","author":"Gandhi","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.bja.2020.06.013","article-title":"Covid-19: A complex multisystem clinical syndrome","volume":"125","author":"Roberts","year":"2020","journal-title":"Br. J. Anaesth."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1056\/NEJMc2008597","article-title":"Neurologic features in severe SARS-CoV-2 infection","volume":"382","author":"Helms","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41586-020-2196-x","article-title":"Virological assessment of hospitalized patients with COVID-2019","volume":"581","author":"Corman","year":"2020","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1007\/s00405-020-05965-1","article-title":"Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multi-center European study","volume":"277","author":"Lechien","year":"2020","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/path.4461","article-title":"The olfactory nerve: A shortcut for influenza and other viral diseases into the central nervous system","volume":"235","author":"Verdijk","year":"2015","journal-title":"J. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.cell.2020.04.035","article-title":"SARS-CoV-2 Receptor ACE2 is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and is detected in Specific Cell Subsets Across Tissues","volume":"181","author":"Ziegler","year":"2020","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41593-020-00758-5","article-title":"Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19","volume":"24","author":"Meinhardt","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/978-81-322-1777-0_6","article-title":"Neuroinvasive and neurotropic human respiratory coronaviruses: Potential neurovirulent agents in humans","volume":"Volume 807","author":"Adhikari","year":"2014","journal-title":"Infectious Diseases and Nanomedicine I"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1756286420917830","DOI":"10.1177\/1756286420917830","article-title":"Potential neurological symptoms of COVID-19","volume":"13","author":"Wang","year":"2020","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1126\/science.1683005","article-title":"PreB\u00f6tzinger complex: A brainstem region that may generate respiratory rhythm in mammals","volume":"254","author":"Smith","year":"1991","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.celrep.2012.09.013","article-title":"The H3K27 demethylase JMJD3 is required for maintenance of the embryonic respiratory neuronal network, neonatal breathing, and survival","volume":"2","author":"Burgold","year":"2012","journal-title":"Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/jmv.25960","article-title":"Comment on \u201cThe neuroinvasive potential of SARS-CoV-2 may play a role in the respiratory failure of COVID-19 patients\u201d","volume":"92","author":"Chigr","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3389\/fncel.2014.00198","article-title":"Modulation of orexigenic and anorexigenic peptides gene expression in the rat DVC and hypothalamus by acute immobilization stress","volume":"8","author":"Chigr","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ejphar.2013.08.047","article-title":"the role of vagal neurocircuits in the regulation of nausea and vomiting","volume":"722","author":"Babic","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/S0025-6196(12)62272-1","article-title":"The central autonomic network: Functional organization, dysfunction, and perspective","volume":"68","author":"Benarroch","year":"1993","journal-title":"Mayo Clin. Proc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jmv.25688","article-title":"The 2019-new coronavirus epidemic: Evidence for virus evolution","volume":"92","author":"Benvenuto","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1126\/science.abd3072","article-title":"Neuropilin-1 is a host factor for SARS-CoV-2 infection","volume":"370","author":"Daly","year":"2020","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.abd2985","article-title":"Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity","volume":"370","author":"Ojha","year":"2020","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Molina-Mora, J.A., Gonz\u00e1lez, A., Jim\u00e9nez-Morgan, S., Cordero-Laurent, E., Brenes, H., Soto-Garita, C., Sequeira-Soto, J., and Duarte-Mart\u00ednez, F. (2021). Clinical profiles at the time of diagnosis of COVID-19 in Costa Rica during the pre-vaccination period using a machine learning approach. medRxiv.","DOI":"10.1101\/2021.06.18.21259157"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Molina-Mora, J.A., Gonz\u00e1lez, A., Jim\u00e9nez-Morgan, S., Cordero-Laurent, E., Brenes, H., Soto-Garita, C., Sequeira-Soto, J., and Duarte-Mart\u00ednez, F. (2022). Metagenomic Pipeline for Identifying Co-Infections among Distinct SARS-CoV-2 Variants of Concern: Study Cases from Alpha to Omicron, Research Square.","DOI":"10.21203\/rs.3.rs-1389767\/v1"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101554","DOI":"10.1016\/j.genrep.2022.101554","article-title":"Insights into the mutation T1117I in the spike and the lineage B.1.1.389 of SARS-CoV-2 circulating in Costa Rica","volume":"27","year":"2022","journal-title":"Gene Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2045-8118-12-4","article-title":"Differential responses of blood-brain barrier associated cells to hypoxia and ischemia: A comparative study","volume":"12","author":"Engelhardt","year":"2015","journal-title":"Fluids Barriers CNS"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.tins.2020.12.002","article-title":"Blood\u2013Brain Barrier Dynamics to Maintain Brain Homeostasis","volume":"44","author":"Segarra","year":"2021","journal-title":"Trends Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2174\/156720208783565645","article-title":"Blood brain barrier in hypoxic-ischemic conditions","volume":"5","author":"Kaur","year":"2008","journal-title":"Curr. Neurovascular Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1093\/eurheartj\/ehaa706","article-title":"Understanding COVID-19: In the end it is the endothelium\u2014What else?","volume":"41","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e00911","DOI":"10.1002\/prp2.911","article-title":"\u201cLONG COVID\u201d\u2014A hypothesis for understanding the biological basis and pharmacological treatment strategy","volume":"10","author":"Jarrott","year":"2022","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1093\/cid\/ciaa345","article-title":"Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients","volume":"71","author":"Yu","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ijid.2020.02.050","article-title":"Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests","volume":"93","author":"Xie","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101673","DOI":"10.1016\/j.tmaid.2020.101673","article-title":"Detection and analysis of nucleic acid in various biological samples of COVID-19 patients","volume":"37","author":"Wu","year":"2020","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"181","DOI":"10.12688\/wellcomeopenres.16002.2","article-title":"SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus","volume":"5","author":"Andersson","year":"2020","journal-title":"Wellcome Open Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e20202135","DOI":"10.1084\/jem.20202135","article-title":"Neuroinvasion of SARS-CoV-2 in human and mouse brain","volume":"218","author":"Song","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.stemcr.2021.12.011","article-title":"The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2","volume":"17","author":"Krasemann","year":"2022","journal-title":"Stem Cell Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.omtn.2021.12.034","article-title":"SARS-CoV-2 Causes a Significant Stress Response Mediated by Small RNAs in the Blood of COVID-19 Patients","volume":"27","author":"Liu","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1136\/bmj.1.4667.1383","article-title":"Stress and the General Adaptation Syndrome","volume":"1","author":"Selye","year":"1950","journal-title":"Br. Med. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1523\/JNEUROSCI.0733-19.2019","article-title":"Revisiting the Stress Concept: Implications for Affective Disorders","volume":"40","author":"McEwen","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1126\/science.6166045","article-title":"Power spectrum analysis of heart rate fluctuation: A quantitative probe of beat-to-beat cardiovascular control","volume":"213","author":"Akselrod","year":"1981","journal-title":"Science"},{"key":"ref_51","first-page":"7:001728","article-title":"Respiratory Distress in SARS-CoV-2 without Lung Damage: Phrenic Paralysis Should Be Considered in COVID-19 Infection","volume":"21","author":"Maurier","year":"2020","journal-title":"Eur. J. Case Rep. Intern. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1056\/NEJM198604103141505","article-title":"A long-term follow-up study of patients with post-poliomyelitis neuromuscular symptoms","volume":"314","author":"Dalakas","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1056\/NEJMoa022450","article-title":"One-Year Outcomes In Survivors Of The Acute Respiratory Distress Syndrome","volume":"348","author":"Herridge","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Moldofsky, H., and Patcai, J. (2011). Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol., 11.","DOI":"10.1186\/1471-2377-11-37"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S2215-0366(21)00084-5","article-title":"6-month neurological and psychiatric outcomes in 236,379 survivors of COVID-19: A retrospective cohort study using electronic health records","volume":"8","author":"Taquet","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/acn3.51350","article-title":"Persistent Neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 \u201clong haulers\u201d","volume":"8","author":"Graham","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.mayocp.2012.08.013","article-title":"Postural tachycardia syndrome: A heterogeneous and multifactorial disorder","volume":"87","author":"Benarroch","year":"2012","journal-title":"Mayo Clin. Proc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1159\/000059054","article-title":"Effect of isobaric oxygen versus hyperbaric oxygen on the normal and noise-damaged hypoxic and ischemic guinea pig inner ear","volume":"54","author":"Lamm","year":"1998","journal-title":"Hyperb. Oxyg. Ther. Otorhinolaryngol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1177\/088506668900400204","article-title":"Hyperbaric oxygen therapy","volume":"4","author":"Thom","year":"1989","journal-title":"J. Intensive Care Med."},{"key":"ref_60","unstructured":"James, P.B. (2014). The Ultimate Oxygen Machine. Oxygen and the Brain: The Journey of Our Lifetime the Brain, Best Publishing Company."},{"key":"ref_61","first-page":"235","article-title":"Effects of hyperbaric oxygen therapy on children with spastic diplegic cerebral palsy: A pilot project","volume":"26","author":"Montgomery","year":"1999","journal-title":"Undersea Hyperb. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1748-1716.1966.tb03281.x","article-title":"The alveolar-arterial oxygen difference: Its size and components in normal man","volume":"67","author":"Mellemgaard","year":"1966","journal-title":"Acta Physiol. Scand."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1093\/bja\/37.12.898","article-title":"Factors influencing the arterial oxygen tension during anaesthesia with artificial ventilation","volume":"37","author":"Nunn","year":"1965","journal-title":"Br. J. Anaesth."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1152\/ajplegacy.1944.142.5.700","article-title":"The oxygen tension of arterial blood and alveolar air in normal subjects","volume":"142","author":"Comroe","year":"1944","journal-title":"Am. J. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1164\/ajrccm.160.5.9806006","article-title":"Arterial bood gas reference values for sea level and an altitude of 1400 m","volume":"160","author":"Crapo","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_66","first-page":"1","article-title":"Partial pressure of oxygen in the human body: A general review","volume":"9","author":"Dunn","year":"2019","journal-title":"Am. J. Blood Res."},{"key":"ref_67","first-page":"734","article-title":"British Thoracic Society Guideline for emergency oxygen use in adult patients","volume":"63","author":"Howard","year":"2008","journal-title":"Thorax"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1056\/NEJMe1504852","article-title":"Saving Lives with High-Flow Nasal Oxygen","volume":"372","author":"Matthay","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1136\/thx.47.8.609","article-title":"Variability of inspired oxygen concentration with nasal cannulas","volume":"47","author":"Bazuaye","year":"1992","journal-title":"Thorax"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1136\/bmj.1.2928.181","article-title":"The therapeutic administration of oxygen","volume":"1","author":"Haldane","year":"1917","journal-title":"Br. Med. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1093\/bja\/50.2.91","article-title":"Detection and reversal of pulmonary absorption collapse","volume":"50","author":"Nunn","year":"1978","journal-title":"Br. J. Anaesth."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1002\/cphy.c110030","article-title":"Ventilatory failure, ventilator support, and ventilator weaning","volume":"2","author":"Tobin","year":"2012","journal-title":"Compr. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1164\/rccm.202004-1076ED","article-title":"Basing respiratory management of COVID-19 on physiological principles","volume":"201","author":"Tobin","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"61","DOI":"10.4103\/2045-9912.282177","article-title":"Hyperbaric oxygen treatment of novel coronavirus (COVID-19) respiratory failure","volume":"10","author":"Harch","year":"2020","journal-title":"Med. Gas Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/bja\/37.1.3","article-title":"Hypoxaemia and atelectasis produced by forced inspiration","volume":"37","author":"Nunn","year":"1965","journal-title":"Brit. J. Anaesth."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"462","DOI":"10.2307\/1297527","article-title":"Oxygen is Toxic!","volume":"27","author":"Fridovich","year":"1977","journal-title":"Bioscience"},{"key":"ref_77","first-page":"255","article-title":"Hypoxia and oxygen toxicity","volume":"26","author":"Fridovich","year":"1979","journal-title":"Adv. Neurol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S0140-6736(02)78146-4","article-title":"Notes of effects experienced during recent balloon ascents","volume":"80","author":"Glaisher","year":"1862","journal-title":"Lancet"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10877-017-0015-1","article-title":"A validation method for near-infrared spectroscopy based tissue oximeters for cerebral and somatic tissue oxygen saturation measurements","volume":"32","author":"Benni","year":"2018","journal-title":"J. Clin. Monit. Comput."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"63","DOI":"10.4103\/2045-9912.285557","article-title":"Intermittent high dosage oxygen treats COVID-19 infection: The Chinese studies","volume":"10","author":"James","year":"2020","journal-title":"Med. Gas Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.12968\/jowc.2020.29.Sup5a.S4","article-title":"Hyperbaric oxygen therapy in preventing mechanical ventilation in COVID-19 patients: A retrospective case series","volume":"29","author":"Thibodeaux","year":"2020","journal-title":"J. Wound Care"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"110224","DOI":"10.1016\/j.mehy.2020.110224","article-title":"Can hyperbaric oxygen safely serve as an anti-inflammatory treatment for COVID-19?","volume":"144","author":"Kjellberg","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"181","DOI":"10.22462\/04.06.2020.2","article-title":"Hyperbaric oxygen therapy may be effective to improve hypoxemia in patients with severe COVID-2019 pneumonia: Two case reports","volume":"47","author":"Guo","year":"2020","journal-title":"Undersea Hyperb. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"405","DOI":"10.22462\/03.07.2020.1","article-title":"Hyperbaric oxygen therapy for COVID-19 patients with respiratory distress: Treated cases versus propensity-matched controls","volume":"47","author":"Gorenstein","year":"2020","journal-title":"Undersea Hyperb. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"271","DOI":"10.28920\/dhm51.3.271-281","article-title":"Efficacy and safety of hyperbaric oxygen treatment in SARS-COV-2 (COVID-19) pneumonia: A systematic review","volume":"51","author":"Boet","year":"2021","journal-title":"Diving Hyperb. Med. J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/emermed-2021-211253","article-title":"Hyperbaric oxygen as an adjuvant treatment for patients with COVID-19 severe hypoxaemia: A randomised controlled trial","volume":"39","author":"Cannellotto","year":"2022","journal-title":"Emerg. Med. J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e629","DOI":"10.7861\/clinmed.2021-0462","article-title":"Hyperbaric oxygen therapy for the treatment of long COVID: Early evaluation of a highly promising intervention","volume":"21","author":"Robbins","year":"2021","journal-title":"Clin. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13256-022-03287-w","article-title":"Hyperbaric oxygen treatment for long coronavirus disease-19: A case report","volume":"16","author":"Bhaiyat","year":"2022","journal-title":"J. Med. Case Rep."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Fischer, I., and Barak, B. (2020). Molecular and Therapeutic Aspects of Hyperbaric Oxygen Therapy in Neurological Conditions. Biomolecules, 10.","DOI":"10.3390\/biom10091247"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Efrati, S., Fishlev, G., Bechor, Y., Volkov, O., Bergan, J., Kliakhandler, K., Kamiager, I., Gal, N., Friedman, M., and Ben-Jacob, E. (2013). Hyperbaric oxygen induces late neuroplasticity in post stroke patients\u2014randomized, prospective trial. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053716"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Boussi-Gross, R., Golan, H., Fishlev, G., Bechor, Y., Volkov, O., Bergan, J., Friedman, M., Hoofien, D., Shlamkovitch, N., and Ben-Jacob, E. (2013). Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury\u2014Randomized prospective trial. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079995"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1586\/14737175.2014.884928","article-title":"Reflections on the neurotherapeutic effects of hyperbaric oxygen","volume":"14","author":"Efrati","year":"2014","journal-title":"Expert Rev. Neurother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1037\/neu0000149","article-title":"Improvement of memory impairments in poststroke patients by hyperbaric oxygen therapy","volume":"29","author":"Golan","year":"2015","journal-title":"Neuropsychology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s12026-015-8718-1","article-title":"Neural circuitry and immunity","volume":"63","author":"Pavlov","year":"2015","journal-title":"Immunol. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2010.02.029","article-title":"Nonresolving inflammation","volume":"140","author":"Nathan","year":"2010","journal-title":"Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1007\/s00213-016-4218-9","article-title":"Stress and neuroinflammation: A systematic review of the effects of stress on microglia and the implications for mental illness","volume":"233","author":"Calcia","year":"2016","journal-title":"Psychopharmacology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1212\/WNL.59.6_suppl_4.S3","article-title":"Therapeutic mechanisms of vagus nerve stimulation","volume":"59","author":"Henry","year":"2002","journal-title":"Neurology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/nn1944","article-title":"Targeting abnormal neural circuits in mood and anxiety disorders: From the laboratory to the clinic","volume":"10","author":"Ressler","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Cao, J., Lu, K.-H., Powley, T.L., and Liu, Z. (2017). Vagal nerve stimulation triggers widespread responses and alters large-scale functional connectivity in the rat brain. PLoS ONE, 12.","DOI":"10.1101\/200220"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.cell.2018.05.005","article-title":"Neurons Are the Inflammatory Problem","volume":"173","author":"Tracey","year":"2018","journal-title":"Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1007\/s00702-007-0755-z","article-title":"BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation","volume":"114","author":"Kraus","year":"2007","journal-title":"J. Neural. Transm."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.brs.2014.11.018","article-title":"Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans","volume":"8","author":"Frangos","year":"2015","journal-title":"Brain Stimul."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nrcardio.2015.2","article-title":"Inflammation and the pathogenesis of atrial fibrillation","volume":"12","author":"Hu","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jacep.2019.11.008","article-title":"TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial","volume":"6","author":"Stavrakis","year":"2020","journal-title":"Clin. Electrophysiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.brs.2019.02.003","article-title":"The influence of respiration on brainstem and cardiovagal response to auricular vagus nerve stimulation: A multimodal ultrahigh-field (7T) fMRI study","volume":"12","author":"Sclocco","year":"2019","journal-title":"Brain Stimul."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"397","DOI":"10.3389\/fnhum.2018.00397","article-title":"Breath of Life: The Respiratory Vagal Stimulation Model of Contemplative Activity","volume":"12","author":"Gerritsen","year":"2018","journal-title":"Front. Hum. Neurosci."},{"key":"ref_107","first-page":"100011","article-title":"Transcutaneous Auricular Vagus Nerve Stimulation (tVNS) can Reverse the Manifestations of the Long-COVID Syndrome: A Pilot Study","volume":"2","author":"Verbanck","year":"2021","journal-title":"Front. Neurology Neurosci. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"570196","DOI":"10.3389\/fpsyg.2020.570196","article-title":"Stress and Tinnitus; Transcutaneous Auricular Vagal Nerve Stimulation Attenuates Tinnitus-Triggered Stress Reaction","volume":"11","author":"Ylikoski","year":"2020","journal-title":"Front. Psychol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1056\/NEJMc1309747","article-title":"Acute high-altitude illnesses","volume":"369","author":"Basnyat","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1378\/chest.07-0561","article-title":"Illnesses at high altitude","volume":"134","author":"Schoene","year":"2008","journal-title":"Chest"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1539\/joh.13-0256-RA","article-title":"High-altitude pulmonary edema: Review","volume":"56","author":"Bhagi","year":"2014","journal-title":"J. Occup. Health"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1113\/jphysiol.1895.sp000578","article-title":"The action of carbonic oxide on man","volume":"18","author":"Haldane","year":"1895","journal-title":"J. Physiol."},{"key":"ref_113","unstructured":"(2010). WHO Guidelines for Indoor Air Quality: Selected PollutantsCarbon Monoxide, World Health Organization."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"665821","DOI":"10.3389\/fphys.2021.665821","article-title":"Hypoxic Hypoxia and Brain Function in Military Aviation: Basic Physiology and Applied Perspectives","volume":"12","author":"Shaw","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/nyas.12719","article-title":"Early history of high-altitude physiology","volume":"1365","author":"West","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s11065-004-8159-4","article-title":"Neuropsychological functioning associated with high-altitude exposure","volume":"14","author":"Garrido","year":"2004","journal-title":"Neuropsychol. Rev."},{"key":"ref_117","first-page":"87","article-title":"Chronic mountain sickness","volume":"139","author":"Monge","year":"1976","journal-title":"Johns Hopkins Med. J."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1056\/NEJMoa2008457","article-title":"Presymptomatic SARS-CoV-2 infections and transmission in a nursing facility","volume":"382","author":"Arons","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/ane.13266","article-title":"Neurological manifestations of COVID-19: A systematic review and current update","volume":"142","author":"Whittaker","year":"2020","journal-title":"Acta Neurol. Scand."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/ane.13399","article-title":"Neurological manifestations as primary presentation of COVID-19 in hospitalized patients","volume":"143","author":"Chuang","year":"2021","journal-title":"Acta Neurol. Scand."},{"key":"ref_121","unstructured":"WHO (2020, November 20). Naming the Coronavirus Disease (COVID-19) and the Virus that Causes it. Available online: https:\/\/www.who.int\/emergencies\/diseases\/novel-coronavirus-2019\/technical-guidance\/naming-the-coronavirus-disease-(COVID-2019)-and-the-virus-that-causes-it\/."},{"key":"ref_122","first-page":"e1060","article-title":"Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry","volume":"95","year":"2020","journal-title":"Neurology"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1001\/jama.2020.6775","article-title":"Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area","volume":"323","author":"Richardson","year":"2020","journal-title":"JAMA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/0006-8993(86)91038-3","article-title":"Rapid increase in blood-brain barrier permeability during severe hypoxia and metabolic inhibition","volume":"368","author":"Olesen","year":"1986","journal-title":"Brain Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"9766","DOI":"10.1038\/s41598-020-66487-8","article-title":"Multicellular 3D Neurovascular Unit Model for Assessing Hypoxia and Neuroinflammation Induced Blood-Brain Barrier Dysfunction","volume":"10","author":"Nzou","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0034-5687(00)00109-2","article-title":"Pulmonary oedema induced by strenuous swimming: A field study","volume":"121","author":"Shupak","year":"2000","journal-title":"Respir. Physiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1378\/chest.126.2.394","article-title":"Swimming-induced pulmonary edema: Clinical presentation and serial lung function","volume":"126","author":"Adir","year":"2004","journal-title":"Chest"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1378\/chest.120.5.1686","article-title":"Pulmonary edema associated with scuba diving: Case reports and review","volume":"120","author":"Slade","year":"2001","journal-title":"Chest"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"968152","DOI":"10.1155\/2015\/968152","article-title":"Exercise-Induced Pulmonary Edema in a Triathlon","volume":"2015","author":"Yamanashi","year":"2015","journal-title":"Case Rep. Med."},{"key":"ref_130","first-page":"131","article-title":"Non-cardiogenic pulmonary edema complicating electroconvulsive therapy: Short review of the pathophysiology and diagnostic approach Clin","volume":"10","author":"Manne","year":"2012","journal-title":"Med. Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1002\/ccr3.3139","article-title":"Seizure followed by lung edema: An intriguing link between the brain and the lung","volume":"8","author":"Arakaki","year":"2020","journal-title":"Clin. Case Rep."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1016\/j.annfar.2012.04.013","article-title":"Interaction brain-lungs","volume":"31","author":"Abdennour","year":"2012","journal-title":"Ann. Fr. D\u2019anesthesie Reanim."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"101754","DOI":"10.1016\/j.tmaid.2020.101754","article-title":"Comparison of clinical and epidemiological characteristics of asymptomatic and symptomatic SARS-CoV-2 infection: A multi-center study in Sichuan Province, China","volume":"37","author":"Kong","year":"2020","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"E30","DOI":"10.1148\/radiol.2020202708","article-title":"Diagnostic performance of chest CT for SARS-CoV-2 infection in individuals with or without COVID-19 symptoms","volume":"298","author":"Ryckaert","year":"2021","journal-title":"Radiology"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.clinimag.2021.01.030","article-title":"Chest CT findings in RT-PCR positive asymptomatic COVID-19 patients","volume":"77","author":"Uysal","year":"2021","journal-title":"Clin. Imaging"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1378\/chest.113.3.571","article-title":"Rehabilitation of hypoxemic patients with COPD at low altitude at the Dead Sea, the lowest place on earth","volume":"113","author":"Kramer","year":"1998","journal-title":"Chest"},{"key":"ref_137","first-page":"806","article-title":"Effects of rehabilitation winter camps at the Dead Sea on European cystic fibrosis patients","volume":"9","author":"Goldbart","year":"2007","journal-title":"Isr. Med. Assoc. J."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/5\/754\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:15:00Z","timestamp":1760138100000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/5\/754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,19]]},"references-count":137,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["life12050754"],"URL":"https:\/\/doi.org\/10.3390\/life12050754","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,19]]}}}