{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T02:14:57Z","timestamp":1784945697725,"version":"3.55.0"},"posted":{"date-parts":[[2021,1,13]]},"group-title":"Pathology","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,9,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Animal models recapitulating distinctive features of severe COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. The precise mechanisms of lethality in this mouse model remain unclear. Here, we evaluated the spatiotemporal dynamics of SARS-CoV-2 infection for up to 14 days post-infection. Despite infection and moderate pneumonia, rapid clinical decline or death of mice was invariably associated with viral neuroinvasion and direct neuronal injury (including brain and spinal neurons). Neuroinvasion was observed as early as 4 dpi, with virus initially restricted to the olfactory bulb supporting axonal transport via the olfactory neuroepithelium as the earliest portal of entry. No evidence of viremia was detected suggesting neuroinvasion occurs independently of entry across the blood brain barrier. SARS-CoV-2 tropism was not restricted to ACE2-expressing cells (e.g., AT1 pneumocytes), and some ACE2-positive lineages were not associated with the presence of viral antigen (e.g., bronchiolar epithelium and brain capillaries). Detectable ACE2 expression was not observed in neurons, supporting overexpression of ACE2 in the nasal passages and neuroepithelium as more likely determinants of neuroinvasion in the K18-hACE2 model. Although our work incites caution in the utility of the K18-hACE2 model to study global aspects of SARS-CoV-2 pathogenesis, it underscores this model as a unique platform for exploring the mechanisms of SARS-CoV-2 neuropathogenesis that may have clinical relevance acknowledging the growing body of evidence that suggests COVID-19 may result in long-standing neurologic consequences.<\/jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>COVID-19 is predominantly a respiratory disease caused by SARS-CoV-2 that has infected more than 191 million people with over 4 million fatalities (2021-07-20). The development of animal models recapitulating distinctive features of severe COVID-19 is critical to enhancing our understanding of SARS-CoV-2 pathogenesis and in the evaluation of vaccine and therapeutic efficacy. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. Here, we show lethality of this model is invariably associated with viral neuroinvasion linked with viral replication and assembly. Importantly, pneumonia albeit invariably present was generally moderate with the absence of culturable infectious virus at peak neuroinvasion. The dynamics of viral neuroinvasion and pneumonia were only partially dependent on hACE2. Overall, this study provides an in-depth sequential characterization of the K18-hACE2 model following SARS-CoV-2 infection, highlighting its significance to further study the mechanisms of SARS-CoV-2 neuropathogenesis.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2021.01.13.425144","type":"posted-content","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T20:47:13Z","timestamp":1610657233000},"source":"Crossref","is-referenced-by-count":30,"title":["Fatal neuroinvasion and SARS-CoV-2 tropism in K18-hACE2 mice is partially independent on hACE2 expression"],"prefix":"10.64898","author":[{"given":"Mariano","family":"Carossino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Montanaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoife","family":"O\u2019Connell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Kenney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Gertje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle A.","family":"Grosz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ericsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand R","family":"Huber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna A.","family":"Kurnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saravanan","family":"Subramaniam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Kirkland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel R.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin P.","family":"Francis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander D.","family":"Klose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal","family":"Paragas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Bosmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsan","family":"Saeed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udeni B. R.","family":"Balasuriya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Douam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3873-9188","authenticated-orcid":false,"given":"Nicholas A.","family":"Crossland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024080508594602000_2021.01.13.425144v3.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0820-9"},{"key":"2024080508594602000_2021.01.13.425144v3.2","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s41564-020-0695-z","article-title":"The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2","volume":"5","author":"Coronaviridae Study Group of the International Committee on Taxonomy of V","year":"2020","journal-title":"Nat Microbiol"},{"key":"2024080508594602000_2021.01.13.425144v3.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30185-9"},{"key":"2024080508594602000_2021.01.13.425144v3.4","unstructured":"Johns Hopkins University & Medicine. 2020. Coronavirus Resource Center. https:\/\/coronavirus.jhu.edu. Accessed"},{"key":"2024080508594602000_2021.01.13.425144v3.5","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1056\/NEJMc2010419","article-title":"Clinical Characteristics of Covid-19 in New York City","volume":"382","year":"2020","journal-title":"N Engl J Med"},{"key":"2024080508594602000_2021.01.13.425144v3.6","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6930e1"},{"key":"2024080508594602000_2021.01.13.425144v3.7","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.928996"},{"key":"2024080508594602000_2021.01.13.425144v3.8","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1002\/oby.22831","article-title":"High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation","volume":"28","author":"Licorn, the Lille C, Obesity study g","year":"2020","journal-title":"Obesity (Silver Spring)"},{"key":"2024080508594602000_2021.01.13.425144v3.9","doi-asserted-by":"crossref","unstructured":"Tartof SY , Qian L , Hong V , Wei R , Nadjafi RF , Fischer H , Li Z , Shaw SF , Caparosa SL , Nau CL , Saxena T , Rieg GK , Ackerson BK , Sharp AL , Skarbinski J , Naik TK , Murali SB. 2020. Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization. Ann Intern Med In press (https:\/\/doi.org\/10.7326\/M20-3742).","DOI":"10.7326\/M20-3742"},{"key":"2024080508594602000_2021.01.13.425144v3.10","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6913e2"},{"key":"2024080508594602000_2021.01.13.425144v3.11","doi-asserted-by":"crossref","unstructured":"DosSantos MF , Devalle S , Aran V , Capra D , Roque NR , Coelho-Aguiar JdM , Spohr TCLdSe , Subilhaga JG , Pereira CM , D\u2019Andrea Meira I , Niemeyer Soares Filho P , Moura-Neto V. 2020. Neuromechanisms of SARS-CoV-2: A Review. Frontiers in Neuroanatomy 14.","DOI":"10.3389\/fnana.2020.00037"},{"key":"2024080508594602000_2021.01.13.425144v3.12","first-page":"e3145","article-title":"Loss of smell in patients with COVID-19: MRI data reveal a transient edema of the olfactory clefts","volume":"95","year":"2020","journal-title":"Neurology"},{"key":"2024080508594602000_2021.01.13.425144v3.13","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30221-0"},{"key":"2024080508594602000_2021.01.13.425144v3.14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2033369"},{"key":"2024080508594602000_2021.01.13.425144v3.15","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26570"},{"key":"2024080508594602000_2021.01.13.425144v3.16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2019373"},{"key":"2024080508594602000_2021.01.13.425144v3.17","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m2808"},{"key":"2024080508594602000_2021.01.13.425144v3.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00758-5"},{"key":"2024080508594602000_2021.01.13.425144v3.19","doi-asserted-by":"crossref","unstructured":"Song E , Zhang C , Israelow B , Lu-Culligan A , Prado AV , Skriabine S , Lu P , Weizman OE , Liu F , Dai Y , Szigeti-Buck K , Yasumoto Y , Wang G , Castaldi C , Heltke J , Ng E , Wheeler J , Alfajaro MM , Levavasseur E , Fontes B , Ravindra NG , Van Dijk D , Mane S , Gunel M , Ring A , Kazmi SAJ , Zhang K , Wilen CB , Horvath TL , Plu I , Haik S , Thomas JL , Louvi A , Farhadian SF , Huttner A , Seilhean D , Renier N , Bilguvar K , Iwasaki A. 2021. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med 218.","DOI":"10.1084\/jem.20202135"},{"key":"2024080508594602000_2021.01.13.425144v3.20","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/s41385-020-00340-z","article-title":"Animal and translational models of SARS-CoV-2 infection and COVID-19","volume":"13","year":"2020","journal-title":"Mucosal Immunol"},{"key":"2024080508594602000_2021.01.13.425144v3.21","doi-asserted-by":"publisher","DOI":"10.1089\/vbz.2020.2650"},{"key":"2024080508594602000_2021.01.13.425144v3.22","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s41586-020-2787-6","article-title":"Animal models for COVID-19","volume":"586","year":"2020","journal-title":"Nature"},{"key":"2024080508594602000_2021.01.13.425144v3.23","doi-asserted-by":"crossref","unstructured":"Gaudreault N , Trujillo J , Carossino M , Meekins D , Madden D , Balaraman V , Henningson J , Morozov I , Bold D , Kwong T , Roman-Sosa G , Artiaga B , Indran S , Cool K , Garcia-Sastre A , Ma W , Wilson W , Balasuriya U , Richt J. 2020. SARS-CoV-2 infection, disease and transmission in domestic cats. Emerg Microbes Inf In press (https:\/\/doi.org\/10.1080\/22221751.2020.1833687).","DOI":"10.1101\/2020.08.04.235002"},{"key":"2024080508594602000_2021.01.13.425144v3.24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2009799117"},{"key":"2024080508594602000_2021.01.13.425144v3.25","doi-asserted-by":"crossref","unstructured":"Meekins DA , Morozov I , Trujillo JD , Gaudreault NN , Bold D , Carossino M , Artiaga BL , Indran SV , Kwon T , Balaraman V , Madden DW , Feldmann H , Henningson J , Ma W , Balasuriya UBR , Richt JA. 2020. Susceptibility of swine cells and domestic pigs to SARS-CoV-2. Emerg Microbes Inf In press (https:\/\/doi.org\/10.1080\/22221751.2020.1831405).","DOI":"10.1101\/2020.08.15.252395"},{"key":"2024080508594602000_2021.01.13.425144v3.26","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb7314"},{"key":"2024080508594602000_2021.01.13.425144v3.27","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb7015"},{"key":"2024080508594602000_2021.01.13.425144v3.28","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwaa291"},{"key":"2024080508594602000_2021.01.13.425144v3.29","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/s41586-020-2342-5","article-title":"Pathogenesis and transmission of SARS-CoV-2 in golden hamsters","volume":"583","year":"2020","journal-title":"Nature"},{"key":"2024080508594602000_2021.01.13.425144v3.30","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/s41590-020-0778-2","article-title":"SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function","volume":"21","year":"2020","journal-title":"Nat Immunol"},{"key":"2024080508594602000_2021.01.13.425144v3.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"2024080508594602000_2021.01.13.425144v3.32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001016"},{"key":"2024080508594602000_2021.01.13.425144v3.33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2010146117"},{"key":"2024080508594602000_2021.01.13.425144v3.34","doi-asserted-by":"crossref","unstructured":"Dinnon KH, 3rd , Leist SR , Schafer A , Edwards CE , Martinez DR , Montgomery SA , West A , Yount BL, Jr. , Hou YJ , Adams LE , Gully KL , Brown AJ , Huang E , Bryant MD , Choong IC , Glenn JS , Gralinski LE , Sheahan TP , Baric RS. 2020. A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures. Nature In press (https:\/\/doi.org\/10.1038\/s41586-020-2708-8).","DOI":"10.1038\/s41586-020-2708-8"},{"key":"2024080508594602000_2021.01.13.425144v3.35","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cell.2020.05.027","article-title":"Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2","volume":"182","year":"2020","journal-title":"Cell"},{"key":"2024080508594602000_2021.01.13.425144v3.36","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02012-06"},{"key":"2024080508594602000_2021.01.13.425144v3.37","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1080\/22221751.2020.1838955","article-title":"Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection","volume":"9","year":"2020","journal-title":"Emerg Microbes Infect"},{"key":"2024080508594602000_2021.01.13.425144v3.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2943-z"},{"key":"2024080508594602000_2021.01.13.425144v3.39","doi-asserted-by":"publisher","DOI":"10.1038\/nature02145"},{"key":"2024080508594602000_2021.01.13.425144v3.40","doi-asserted-by":"crossref","unstructured":"Golden JW , Cline CR , Zeng X , Garrison AR , Carey BD , Mucker EM , White LE , Shamblin JD , Brocato RL , Liu J , Babka AM , Rauch HB , Smith JM , Hollidge BS , Fitzpatrick C , Badger CV , Hooper JW. 2020. Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease. JCI Insight 5.","DOI":"10.1172\/jci.insight.142032"},{"key":"2024080508594602000_2021.01.13.425144v3.41","doi-asserted-by":"crossref","unstructured":"Kumari P , Rothan HA , Natekar JP , Stone S , Pathak H , Strate PG , Arora K , Brinton MA , Kumar M . 2021. Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice. Viruses 13.","DOI":"10.1101\/2020.12.14.422714"},{"key":"2024080508594602000_2021.01.13.425144v3.42","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1007\/s00705-020-04737-w","article-title":"Detection of SARS-CoV-2 by RNAscope((R)) in situ hybridization and immunohistochemistry techniques","volume":"165","year":"2020","journal-title":"Arch Virol"},{"key":"2024080508594602000_2021.01.13.425144v3.43","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.3201\/eid2609.202095","article-title":"Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States","volume":"26","year":"2020","journal-title":"Emerg Infect Dis"},{"key":"2024080508594602000_2021.01.13.425144v3.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2020.10.016"},{"key":"2024080508594602000_2021.01.13.425144v3.45","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/j.cell.2020.10.005","article-title":"Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques","volume":"183","year":"2020","journal-title":"Cell"},{"key":"2024080508594602000_2021.01.13.425144v3.46","doi-asserted-by":"publisher","DOI":"10.1101\/2021.03.22.436337"},{"key":"2024080508594602000_2021.01.13.425144v3.47","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.20-0762"},{"key":"2024080508594602000_2021.01.13.425144v3.48","doi-asserted-by":"crossref","unstructured":"Oladunni FS , Park J-G , Tamayo PP , Gonzalez O , Akhter A , Allu\u00e9-Guardia A , Olmo-Font\u00e1nez A , Gautam S , Garcia-Vilanova A , Ye C , Chiem K , Headley C , Dwivedi V , Parodi LM , Alfson KJ , Staples HM , Schami A , Garcia JI , Whigham A , Platt RN , Gazi M , Martinez J , Chuba C , Earley S , Rodriguez OH , Mdaki SD , Kavelish KN , Escalona R , Hallam CRA , Christie C , Patterson JL , Anderson TJC , Carrion R , Dick EJ , Hall-Ursone S , Schlesinger LS , Kaushal D , Giavedoni LD , Alvarez X , Turner J , Martinez-Sobrido L , Torrelles JB. 2020. Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice. bioRxiv preprint (https:\/\/doi.org\/10.1101\/2020.07.18.210179).","DOI":"10.1038\/s41467-020-19891-7"},{"key":"2024080508594602000_2021.01.13.425144v3.49","doi-asserted-by":"publisher","DOI":"10.1101\/2020.08.11.246314"},{"key":"2024080508594602000_2021.01.13.425144v3.50","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.chom.2020.05.020","article-title":"A Mouse Model of SARS-CoV-2 Infection and Pathogenesis","volume":"28","year":"2020","journal-title":"Cell Host Microbe"},{"key":"2024080508594602000_2021.01.13.425144v3.51","doi-asserted-by":"publisher","DOI":"10.1007\/s12024-020-00310-8"},{"key":"2024080508594602000_2021.01.13.425144v3.52","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.bbi.2020.06.032","article-title":"Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters","volume":"89","year":"2020","journal-title":"Brain Behav Immun"},{"key":"2024080508594602000_2021.01.13.425144v3.53","doi-asserted-by":"crossref","unstructured":"Osterrieder N , Bertzbach LD , Dietert K , Abdelgawad A , Vladimirova D , Kunec D , Hoffmann D , Beer M , Gruber AD , Trimpert J . 2020. Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters. Viruses 12.","DOI":"10.1101\/2020.06.10.144188"},{"key":"2024080508594602000_2021.01.13.425144v3.54","doi-asserted-by":"publisher","DOI":"10.1101\/2020.09.25.314070"},{"key":"2024080508594602000_2021.01.13.425144v3.55","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd2985"},{"key":"2024080508594602000_2021.01.13.425144v3.56","doi-asserted-by":"publisher","DOI":"10.1101\/2021.06.01.446640"},{"key":"2024080508594602000_2021.01.13.425144v3.57","doi-asserted-by":"crossref","unstructured":"Chen M , Shen W , Rowan NR , Kulaga H , Hillel A , Ramanathan M, Jr. , Lane AP . 2020. Elevated ACE-2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication. Eur Respir J 56.","DOI":"10.1101\/2020.05.08.084996"},{"key":"2024080508594602000_2021.01.13.425144v3.58","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03720-y"},{"key":"2024080508594602000_2021.01.13.425144v3.59","doi-asserted-by":"publisher","DOI":"10.1101\/2021.05.03.442520"},{"key":"2024080508594602000_2021.01.13.425144v3.60","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf4058"},{"key":"2024080508594602000_2021.01.13.425144v3.61","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19055-7"},{"key":"2024080508594602000_2021.01.13.425144v3.62","doi-asserted-by":"crossref","unstructured":"Corman VM , Landt O , Kaiser M , Molenkamp R , Meijer A , Chu DK , Bleicker T , Brunink S , Schneider J , Schmidt ML , Mulders DG , Haagmans BL , van der Veer B , van den Brink S , Wijsman L , Goderski G , Romette JL , Ellis J , Zambon M , Peiris M , Goossens H , Reusken C , Koopmans MP , Drosten C. 2020. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill 25.","DOI":"10.2807\/1560-7917.ES.2020.25.3.2000045"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2021.01.13.425144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T01:14:34Z","timestamp":1768439674000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2021.01.13.425144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,13]]},"references-count":62,"URL":"https:\/\/doi.org\/10.1101\/2021.01.13.425144","relation":{},"subject":[],"published":{"date-parts":[[2021,1,13]]},"subtype":"preprint"}}