{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:39:58Z","timestamp":1791333598204,"version":"4.3.1"},"posted":{"date-parts":[[2021,3,12]]},"group-title":"Genetic and Genomic Medicine","reference-count":36,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>There is considerable variability in COVID-19 outcomes amongst younger adults\u2014and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Method<\/jats:title>\n                  <jats:p>The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1\u00b74, 95% confidence interval [CI] 1\u00b72\u20131\u00b76) and COVID-19 related mortality (HR 1\u00b75, 95%CI 1\u00b73\u20131\u00b78). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2\u00b70, 95%CI 1\u00b76-2\u00b76), venous thromboembolism (OR 1\u00b77, 95%CI 1\u00b72-2\u00b74), and hepatic injury (OR 1\u00b76, 95%CI 1\u00b72-2\u00b70). Risk allele carriers \u2264 60 years had higher odds of death or severe respiratory failure (OR 2\u00b76, 95%CI 1\u00b78-3\u00b79) compared to those &gt; 60 years OR 1\u00b75 (95%CI 1\u00b73-1\u00b79, interaction p-value=0\u00b704). Amongst individuals \u2264 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31\u00b78% (95%CI 27\u00b76-36\u00b72) were risk variant carriers, compared to 13\u00b79% (95%CI 12\u00b76-15\u00b72%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those \u2264 60 years improved when including the risk allele (AUC 0\u00b782 vs 0\u00b784, p=0\u00b7016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality\u2014and these are more pronounced amongst individuals \u2264 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>Funding was obtained by each of the participating cohorts individually.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2021.03.07.21252875","type":"posted-content","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T09:45:12Z","timestamp":1615542312000},"source":"Crossref","is-referenced-by-count":18,"title":["Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9510-5646","authenticated-orcid":false,"given":"Tomoko","family":"Nakanishi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-9393","authenticated-orcid":false,"given":"Sara","family":"Pigazzini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Degenhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-0520","authenticated-orcid":false,"given":"Mattia","family":"Cordioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-0396","authenticated-orcid":false,"given":"Guillaume","family":"Butler-Laporte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0669-6526","authenticated-orcid":false,"given":"Douglas","family":"Maya-Miles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4698-5680","authenticated-orcid":false,"given":"Beatriz","family":"Nafr\u00eda-Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1368-6550","authenticated-orcid":false,"given":"Youssef","family":"Bouysran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0696-6175","authenticated-orcid":false,"given":"Mari","family":"Niemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0130-1302","authenticated-orcid":false,"given":"Adriana","family":"Palom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4332-6110","authenticated-orcid":false,"given":"David","family":"Ellinghaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6651-2725","authenticated-orcid":false,"given":"Atlas","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-4487","authenticated-orcid":false,"given":"Manuel","family":"Mart\u00ednez-Bueno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina","family":"Rolker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Amitano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8160-9613","authenticated-orcid":false,"given":"Luisa Roade","family":"Tato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"FinnGen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The COVID-19 Host Genetics Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4363-2353","authenticated-orcid":false,"given":"Francesca","family":"Fava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3875-5367","authenticated-orcid":false,"given":"Christoph D.","family":"Spinner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2281-7498","authenticated-orcid":false,"given":"Daniele","family":"Prati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2843-6696","authenticated-orcid":false,"given":"David","family":"Bernardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8192-1351","authenticated-orcid":false,"given":"Gilles","family":"Darcis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4821-2363","authenticated-orcid":false,"given":"Israel","family":"Fern\u00e1ndez-Cadenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1618-5022","authenticated-orcid":false,"given":"Jan Cato","family":"Holter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Banales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2278-7951","authenticated-orcid":false,"given":"Robert","family":"Frithiof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5047-6715","authenticated-orcid":false,"given":"Krzysztof","family":"Kiryluk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3457-1410","authenticated-orcid":false,"given":"Stefano","family":"Duga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5351-0619","authenticated-orcid":false,"given":"Rosanna","family":"Asselta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7782-5540","authenticated-orcid":false,"given":"Alexandre C","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-8947","authenticated-orcid":false,"given":"Manuel","family":"Romero-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Bujanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5900-8096","authenticated-orcid":false,"given":"Johannes R.","family":"Hov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8972-8211","authenticated-orcid":false,"given":"Isabelle","family":"Migeotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0846-9220","authenticated-orcid":false,"given":"Alessandra","family":"Renieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6147-1880","authenticated-orcid":false,"given":"Anna M.","family":"Planas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-2519","authenticated-orcid":false,"given":"Kerstin U.","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0732-3078","authenticated-orcid":false,"given":"Maria","family":"Buti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0956-0242","authenticated-orcid":false,"given":"Souad","family":"Rahmouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7632-4154","authenticated-orcid":false,"given":"Marta E.","family":"Alarc\u00f3n-Riquelme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3105-5672","authenticated-orcid":false,"given":"Eva C.","family":"Schulte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8289-9931","authenticated-orcid":false,"given":"Tom H","family":"Karlsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8909-0345","authenticated-orcid":false,"given":"Luca","family":"Valenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7118-1249","authenticated-orcid":false,"given":"Hugo","family":"Zeberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-9086","authenticated-orcid":false,"given":"J. Brent","family":"Richards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8147-240X","authenticated-orcid":false,"given":"Andrea","family":"Ganna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2021031509101044000_2021.03.07.21252875v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0863-y"},{"key":"2021031509101044000_2021.03.07.21252875v1.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003346"},{"key":"2021031509101044000_2021.03.07.21252875v1.3","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm695152e2"},{"key":"2021031509101044000_2021.03.07.21252875v1.4","first-page":"140","article-title":"Age-specific mortality and immunity patterns of SARS-CoV-2","volume":"590","year":"2020","journal-title":"Nature"},{"key":"2021031509101044000_2021.03.07.21252875v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2521-4"},{"key":"2021031509101044000_2021.03.07.21252875v1.6","doi-asserted-by":"crossref","first-page":"100464","DOI":"10.1016\/j.eclinm.2020.100464","article-title":"A country level analysis measuring the impact of government actions, country preparedness and socioeconomic factors on COVID-19 mortality and related health outcomes","volume":"25","year":"2020","journal-title":"EClinicalMedicine"},{"key":"2021031509101044000_2021.03.07.21252875v1.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr2032888"},{"key":"2021031509101044000_2021.03.07.21252875v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-010-0805-3"},{"key":"2021031509101044000_2021.03.07.21252875v1.9","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht273"},{"key":"2021031509101044000_2021.03.07.21252875v1.10","unstructured":"Biobank U , Feng Y-CA , Ge T , et al. Findings and insights from the genetic investigation of age of first reported occurrence for complex disorders in the UK Biobank and FinnGen. medRxiv 2020; : 2020.11.20.20234302."},{"key":"2021031509101044000_2021.03.07.21252875v1.11","unstructured":"Ellinghaus D , Degenhardt F , Bujanda L , et al. Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N Engl J Med 2020; : EJMoa2020283."},{"key":"2021031509101044000_2021.03.07.21252875v1.12","doi-asserted-by":"crossref","unstructured":"Pairo-Castineira E , Clohisey S , Klaric L , et al. Genetic mechanisms of critical illness in Covid-19. Nature 2020; : 1\u20131.","DOI":"10.1101\/2020.09.24.20200048"},{"key":"2021031509101044000_2021.03.07.21252875v1.13","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41431-020-0636-6","volume":"28","author":"The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic","year":"2020","journal-title":"Eur J Hum Genet"},{"key":"2021031509101044000_2021.03.07.21252875v1.14","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/s41586-020-2818-3","article-title":"The major genetic risk factor for severe COVID-19 is inherited from Neanderthals","volume":"587","year":"2020","journal-title":"Nature"},{"key":"2021031509101044000_2021.03.07.21252875v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"2021031509101044000_2021.03.07.21252875v1.16","unstructured":"COVID-19 Host Genetics Analysis Plan v1.1 - Google Docs. https:\/\/docs.google.com\/document\/d\/16ethjgi4MzlQeO0KAW_yDYyUHdB9kKbtfuGW4XYVKQg\/edit#heading=h.yvzvdf3jx6u9 (accessed Feb 7, 2021)."},{"key":"2021031509101044000_2021.03.07.21252875v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"2021031509101044000_2021.03.07.21252875v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/nature09298"},{"key":"2021031509101044000_2021.03.07.21252875v1.19","doi-asserted-by":"crossref","unstructured":"Del Valle DM , Kim-Schulze S , Huang H-H , et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med 2020; : 1\u20138.","DOI":"10.1038\/s41591-020-1051-9"},{"key":"2021031509101044000_2021.03.07.21252875v1.20","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/s41584-020-0474-5","article-title":"Emerging evidence of a COVID-19 thrombotic syndrome has treatment implications","volume":"16","year":"2020","journal-title":"Nat. Rev. Rheumatol"},{"key":"2021031509101044000_2021.03.07.21252875v1.21","doi-asserted-by":"crossref","unstructured":"Higuera-de la Tijera F , Serv\u00edn-Caama\u00f1o A , Reyes-Herrera D , et al. Impact of liver enzymes on SARS-CoV-2 infection and the severity of clinical course of COVID-19. Liver Res 2021;published online Jan 12. DOI:10.1016\/j.livres.2021.01.001.","DOI":"10.1016\/j.livres.2021.01.001"},{"key":"2021031509101044000_2021.03.07.21252875v1.22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ajem.2020.12.003","article-title":"Increased age, neutrophil-to-lymphocyte ratio (NLR) and white blood cells count are associated with higher COVID-19 mortality","volume":"40","year":"2021","journal-title":"Am J Emerg Med"},{"key":"2021031509101044000_2021.03.07.21252875v1.23","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s42256-020-0180-7","article-title":"An interpretable mortality prediction model for COVID-19 patients","volume":"2","year":"2020","journal-title":"Nat Mach Intell"},{"key":"2021031509101044000_2021.03.07.21252875v1.24","unstructured":"Donn\u00e9es COVID-19 par \u00e2ge et sexe au Qu\u00e9bec | INSPQ. https:\/\/www.inspq.qc.ca\/covid-19\/donnees\/age-sexe (accessed Feb 14, 2021)."},{"key":"2021031509101044000_2021.03.07.21252875v1.25","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1007\/s00038-020-01486-0","article-title":"Age-specific COVID-19 case-fatality rate: no evidence of changes over time","volume":"65","year":"2020","journal-title":"Int. J. Public Health"},{"key":"2021031509101044000_2021.03.07.21252875v1.26","unstructured":"Certain Medical Conditions and Risk for Severe COVID-19 Illness | CDC. https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/need-extra-precautions\/people-with-medical-conditions.html (accessed Jan 29, 2021)."},{"key":"2021031509101044000_2021.03.07.21252875v1.27","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"2021031509101044000_2021.03.07.21252875v1.28","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-014-1889-6"},{"key":"2021031509101044000_2021.03.07.21252875v1.29","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41392-021-00519-1","article-title":"Genome and epigenome editing identify CCR9 and SLC6A20 as target genes at the 3p21.31 locus associated with severe COVID-19","volume":"6","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"2021031509101044000_2021.03.07.21252875v1.30","doi-asserted-by":"crossref","unstructured":"Smieszek SP , Polymeropoulos MH . Role of FYVE and Coiled-Coil Domain Autophagy Adaptor 1 in severity of COVID-19 1 infection 2. medRxiv 2021; : 2021.01.22.21250070.","DOI":"10.1101\/2021.01.22.21250070"},{"key":"2021031509101044000_2021.03.07.21252875v1.31","doi-asserted-by":"publisher","DOI":"10.1101\/2021.01.25.428125"},{"key":"2021031509101044000_2021.03.07.21252875v1.32","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.csbj.2021.01.034","article-title":"Chemokines and chemokine receptors during COVID-19 infection","volume":"19","year":"2021","journal-title":"Comput. Struct. Biotechnol. J"},{"key":"2021031509101044000_2021.03.07.21252875v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0602-4"},{"key":"2021031509101044000_2021.03.07.21252875v1.34","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/s41591-020-0901-9","article-title":"Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19","volume":"26","year":"2020","journal-title":"Nat Med"},{"key":"2021031509101044000_2021.03.07.21252875v1.35","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwx246"},{"key":"2021031509101044000_2021.03.07.21252875v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13889-6"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2021.03.07.21252875","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:09:31Z","timestamp":1768486171000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2021.03.07.21252875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,12]]},"references-count":36,"URL":"https:\/\/doi.org\/10.1101\/2021.03.07.21252875","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1172\/JCI152386","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2021,3,12]]},"subtype":"preprint"}}