{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:54:27Z","timestamp":1784310867493,"version":"3.55.0"},"reference-count":72,"publisher":"The Royal Society","issue":"6","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Pirbright Institute","award":["BBS\/E\/I\/00007030"],"award-info":[{"award-number":["BBS\/E\/I\/00007030"]}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:p>Coronavirus disease 2019 (COVID-19) was initially considered a primarily respiratory disease but is now known to affect other organs including the heart and brain. A major route by which COVID-19 impacts different organs is via the vascular system. We studied the impact of apolipoprotein E (APOE) genotype and inflammation on vascular infectivity by pseudo-typed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses in mouse and human cultured endothelial cells and pericytes. Possessing the APOE4 allele or having existing systemic inflammation is known to enhance the severity of COVID-19. Using targeted replacement human APOE3 and APOE4 mice and inflammation induced by bacterial lipopolysaccharide (LPS), we investigated infection by SARS-CoV-2. Here, we show that infectivity was higher in murine cerebrovascular pericytes compared to endothelial cells and higher in cultures expressing APOE4. Furthermore, increasing the inflammatory state of the cells by prior incubation with LPS increased infectivity into human and mouse pericytes and human endothelial cells. Our findings provide insights into the mechanisms underlying severe COVID-19 infection, highlighting how risk factors such as APOE4 genotype and prior inflammation may exacerbate disease severity by augmenting the virus\u2019s ability to infect vascular cells.<\/jats:p>","DOI":"10.1098\/rsob.230349","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T19:05:15Z","timestamp":1718132715000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Risk factors for severe COVID-19 disease increase SARS-CoV-2 infectivity of endothelial cells and pericytes"],"prefix":"10.1098","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3274-0559","authenticated-orcid":true,"given":"Luca","family":"Biasetti","sequence":"first","affiliation":[{"name":"Sussex Neuroscience, School of Psychology, University of Sussex , East Sussex BN1 9QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikos","family":"Zervogiannis","sequence":"additional","affiliation":[{"name":"Sussex Neuroscience, School of Psychology, University of Sussex , East Sussex BN1 9QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3889-1171","authenticated-orcid":true,"given":"Kira","family":"Shaw","sequence":"additional","affiliation":[{"name":"Sussex Neuroscience, School of Psychology, University of Sussex , East Sussex BN1 9QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7717-8436","authenticated-orcid":true,"given":"Harry","family":"Trewhitt","sequence":"additional","affiliation":[{"name":"Sussex Neuroscience, School of Psychology, University of Sussex , East Sussex BN1 9QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9335-7751","authenticated-orcid":true,"given":"Louise","family":"Serpell","sequence":"additional","affiliation":[{"name":"Sussex Neuroscience, School of Life Sciences, University of Sussex , East Sussex BN1 9QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5640-2266","authenticated-orcid":true,"given":"Dalan","family":"Bailey","sequence":"additional","affiliation":[{"name":"The Pirbright Institute , Surrey GU24 0NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-5138","authenticated-orcid":true,"given":"Edward","family":"Wright","sequence":"additional","affiliation":[{"name":"Viral Pseudotype Unit, School of Life Sciences, University of Sussex , , East Sussex BN1 9QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2316-7714","authenticated-orcid":true,"given":"Catherine N.","family":"Hall","sequence":"additional","affiliation":[{"name":"Sussex Neuroscience, School of Psychology, University of Sussex , East Sussex BN1 9QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(22)00044-4"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.55965"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0262-4079(22)01045-4"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0267392"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-048391"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-021-09185-5"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.2020-0896"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.200208"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2020.10.005"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0343-0"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-020-01510-0"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050354"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-021-01359-7"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15490"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14726"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI147329"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00221-6"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"e_1_3_8_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00558-8"},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008461"},{"key":"e_1_3_8_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.04.022"},{"key":"e_1_3_8_23_2","article-title":"Pericyte-specific vascular expression of SARS-Cov-2 receptor Ace2 \u2013 implications for Microvascular inflammation and Hypercoagulopathy in COVID-19","author":"He L","year":"2020","unstructured":"He L et al . 2020 Pericyte-specific vascular expression of SARS-Cov-2 receptor Ace2 \u2013 implications for Microvascular inflammation and Hypercoagulopathy in COVID-19. Pathology (doi:10.1101\/2020.05.11.088500)","journal-title":"Pathology"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25739"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111622"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/v13010029"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1570"},{"key":"e_1_3_8_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00926-1"},{"key":"e_1_3_8_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.06.005"},{"key":"e_1_3_8_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep35108"},{"key":"e_1_3_8_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glaa131"},{"key":"e_1_3_8_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.12.018"},{"key":"e_1_3_8_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.15685"},{"key":"e_1_3_8_34_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu12051466"},{"key":"e_1_3_8_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-0320-7_31"},{"key":"e_1_3_8_36_2","first-page":"60588","article-title":"A high output method to isolate cerebral pericytes from mouse","volume":"155","author":"Mehra A","year":"2020","unstructured":"Mehra A , Dehouck L , Vandenhaute E , Fatar M , Fenart L , Gosselet F . 2020 A high output method to isolate cerebral pericytes from mouse. J. Vis. Exp 155 , 60588. (doi:10.3791\/60588)","journal-title":"J. Vis. Exp"},{"key":"e_1_3_8_37_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.2008\/000349-0"},{"key":"e_1_3_8_38_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.110601.135414"},{"key":"e_1_3_8_39_2","unstructured":"DataBase Center for Life Science (DBCLS) . HEK293 cell image [Internet]. Wikimedia Commons: HEK203 cell. See https:\/\/commons.wikimedia.org\/wiki\/File:201101_HEK293.png."},{"key":"e_1_3_8_40_2","unstructured":"Granit R . 96 well plate image. See https:\/\/figshare.com\/articles\/dataset\/96well_plate\/3467216\/1."},{"key":"e_1_3_8_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00127-20"},{"key":"e_1_3_8_42_2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001735"},{"key":"e_1_3_8_43_2","unstructured":"Scidraw . 2020 Mouse top. Zenodo. (doi:10.5281\/zenodo.3925917)"},{"key":"e_1_3_8_44_2","unstructured":"Thompson E . 2020 Mouse brain above and side. Zenodo. (doi:10.5281\/zenodo.3925987)"},{"key":"e_1_3_8_45_2","doi-asserted-by":"publisher","DOI":"10.1515\/labmed-2021-0134"},{"key":"e_1_3_8_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00536-9"},{"key":"e_1_3_8_47_2","doi-asserted-by":"publisher","DOI":"10.1113\/EP090802"},{"key":"e_1_3_8_48_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050907"},{"key":"e_1_3_8_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.052824"},{"key":"e_1_3_8_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03570-8"},{"key":"e_1_3_8_51_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1117845"},{"key":"e_1_3_8_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2022.03.016"},{"key":"e_1_3_8_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01302-7"},{"key":"e_1_3_8_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01118-4"},{"key":"e_1_3_8_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04369-3"},{"key":"e_1_3_8_56_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-03945-7"},{"key":"e_1_3_8_57_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.647990"},{"key":"e_1_3_8_58_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00850-3"},{"key":"e_1_3_8_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2247-3"},{"key":"e_1_3_8_60_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10081545"},{"key":"e_1_3_8_61_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1062491"},{"key":"e_1_3_8_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(21)00247-2"},{"key":"e_1_3_8_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjaa067"},{"key":"e_1_3_8_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjac058"},{"key":"e_1_3_8_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.01.006"},{"key":"e_1_3_8_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11087"},{"key":"e_1_3_8_67_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-020-00773-9"},{"key":"e_1_3_8_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119752"},{"key":"e_1_3_8_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-022-01143-7"},{"key":"e_1_3_8_70_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.027188"},{"key":"e_1_3_8_71_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00189.2022"},{"key":"e_1_3_8_72_2","unstructured":"Biasetti L et al . 2024 Data for: Risk factors for severe COVID-19 disease increase SARS CoV-2 infectivity of endothelial cells and pericytes (doi:10.25377\/sussex.22795940)"},{"key":"e_1_3_8_73_2","unstructured":"Biasetti L Zervogiannis N Trewhitt H Shaw K Serpell L Bailey D et al . 2024 Supplementary material from: Risk Factors for Severe COVID-19 Disease Increase SARS CoV-2 Infectivity of Endothelial Cells and Pericytes. Figshare (doi:10.6084\/m9.figshare.c.7214508)"}],"container-title":["Open Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.230349","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rsob.230349","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.230349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T19:05:35Z","timestamp":1718132735000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rsob.230349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":72,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1098\/rsob.230349"],"URL":"https:\/\/doi.org\/10.1098\/rsob.230349","relation":{"has-review":[{"id-type":"doi","id":"10.1098\/RSOB.230349\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.230349\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.230349\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.230349\/v1\/decision1","asserted-by":"object"}]},"ISSN":["2046-2441"],"issn-type":[{"value":"2046-2441","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"2023-09-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"230349"}}