{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:12:16Z","timestamp":1760148736903,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T00:00:00Z","timestamp":1685318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Pathology of the University of Illinois in Chicago"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may spread to the human brain are poorly understood, and the infection of cancer cells in the brain by SARS-CoV-2 in Coronavirus disease 2019 (COVID-19) patients has been the subject of only one previous case report. Here, we report the detection of SARS-CoV-2 RNA by in situ hybridization in lung-cancer cells metastatic to the brain and adjacent brain parenchyma in a 63-year-old male patient with COVID-19. These findings suggest that metastatic tumors may transport the virus from other parts of the body to the brain or may break down the blood\u2013brain barrier to allow for the virus to spread to the brain. These findings confirm and extend previous observations that cancer cells in the brain can become infected by SARS-CoV-2 in patients with COVID-19 and raise the possibility that SARS-CoV-2 can have a direct effect on cancer growth and outcome.<\/jats:p>","DOI":"10.3390\/pathogens12060772","type":"journal-article","created":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T07:54:16Z","timestamp":1685346856000},"page":"772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Detection of SARS-CoV-2 RNA by In Situ Hybridization in Lung-Cancer Cells Metastatic to Brain and in Adjacent Brain Parenchyma"],"prefix":"10.3390","volume":"12","author":[{"given":"Tibor","family":"Valyi-Nagy","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Fredericks","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sajal Deea","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"},{"name":"Illinois Mathematics and Science Academy, Aurora, IL 60506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suman","family":"Setty","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7946-8639","authenticated-orcid":false,"given":"Konstantin V.","family":"Slavin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"},{"name":"Neurology Section, Jesse Brown Veterans Administration Medical Center, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klara","family":"Valyi-Nagy","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus biology and replication: Implications for SARS-CoV-2","volume":"19","author":"Kratzel","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41579-022-00713-0","article-title":"SARS-CoV-2 pathogenesis","volume":"20","author":"Lamers","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.3201\/eid2606.200239","article-title":"Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Shenzhen, China, 2020","volume":"26","author":"Liu","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/S0140-6736(20)30154-9","article-title":"A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster","volume":"395","author":"Chan","year":"2020","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1056\/NEJMoa2001316","article-title":"Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia","volume":"382","author":"Li","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/s41586-022-05542-y","article-title":"SARS-CoV-2 infection and persistence in the human body and brain at autopsy","volume":"612","author":"Stein","year":"2022","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1126\/science.abm2052","article-title":"Nervous system consequences of COVID-19","volume":"375","author":"Spudich","year":"2022","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S1474-4422(20)30308-2","article-title":"Neuropathology of patients with COVID-19 in Germany: A post-mortem case series","volume":"19","author":"Matschke","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1056\/NEJMc2011400","article-title":"Multiorgan and Renal Tropism of SARS-CoV-2","volume":"383","author":"Puelles","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_11","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_12","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":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1016\/j.immuni.2021.06.002","article-title":"Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions","volume":"54","author":"Schwabenland","year":"2021","journal-title":"Immunity"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1158\/2159-8290.CD-20-0422","article-title":"Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak","volume":"10","author":"Dai","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.lungcan.2020.05.034","article-title":"COVID-19 and lung cancer: A greater fatality rate?","volume":"146","author":"Rogado","year":"2020","journal-title":"Lung Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/S0140-6736(20)31187-9","article-title":"COVID-19 and Cancer Consortium. Clinical impact of COVID-19 on patients with cancer (CCC19): A cohort study","volume":"395","author":"Kuderer","year":"2020","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bungaro, M., Passiglia, F., and Scagliotti, G.V. (2022). COVID-19 and Lung Cancer: A Comprehensive Overview from Outbreak to Recovery. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040776"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5289","DOI":"10.7150\/jca.49462","article-title":"Expression of the SAR2-Cov-2 receptor ACE2 reveals the susceptibility of COVID-19 in non-small cell lung cancer","volume":"11","author":"Zhang","year":"2020","journal-title":"J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ricardo, S., Can\u00e3o, P., Martins, D., Magalh\u00e3es, A.C., Pereira, M., Ribeiro-Junior, U., de Mello, E.S., Alves, V.A., Pinto, R., and Leit\u00e3o, D. (2022). Searching for SARS-CoV-2 in Cancer Tissues: Results of an Extensive Methodologic Approach based on ACE2 and Furin Expression. Cancers, 14.","DOI":"10.3390\/cancers14112582"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1097\/WNR.0000000000001654","article-title":"Evidence for residual SARS-CoV-2 in glioblastoma tissue of a convalescent patient","volume":"32","author":"Lei","year":"2021","journal-title":"Neuroreport"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1136\/jclinpath-2020-206635","article-title":"SARS-CoV-2 detection in formalin-fixed paraffin-embedded tissue specimens from surgical resection of tongue squamous cell carcinoma","volume":"73","author":"Taormina","year":"2020","journal-title":"J. Clin. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1056\/NEJMoa2024671","article-title":"Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates","volume":"383","author":"Corbett","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Babal, P., Krivosikova, L., Sarvaicova, L., Deckov, I., Szemes, T., Sedlackova, T., Palkovic, M., Kalinakova, A., and Janega, P. (2021). Intrauterine Fetal Demise after Uncomplicated COVID-19: What Can We Learn from the Case?. Viruses, 13.","DOI":"10.3390\/v13122545"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jmoldx.2011.08.002","article-title":"RNAscope: A novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues","volume":"14","author":"Wang","year":"2012","journal-title":"J. Mol. Diagn."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/978-3-642-38965-8_2","article-title":"Epidemiology of virus infection and human cancer","volume":"193","author":"Chen","year":"2014","journal-title":"Recent. Results Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4047","DOI":"10.3390\/v6104047","article-title":"Human viruses and cancer","volume":"6","year":"2014","journal-title":"Viruses"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/sj.mt.6300108","article-title":"History of oncolytic viruses: Genesis to genetic engineering","volume":"15","author":"Kelly","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.2217\/imt.13.123","article-title":"Evolution of oncolytic viruses: Novel strategies for cancer treatment","volume":"5","author":"Atherton","year":"2013","journal-title":"Immunotherapy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1200\/PO.20.00395","article-title":"Evolving Role of Oncolytic Virotherapy: Challenges and Prospects in Clinical Practice","volume":"5","author":"Moaven","year":"2021","journal-title":"JCO Precis. Oncol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/6\/772\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:44:20Z","timestamp":1760125460000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/6\/772"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,29]]},"references-count":29,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["pathogens12060772"],"URL":"https:\/\/doi.org\/10.3390\/pathogens12060772","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2023,5,29]]}}}