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provide support and an analytical network for studies that are broadly interested in identifying genetic determinants of COVID-19 susceptibility and severity. Such discoveries could help to generate hypotheses for drug repurposing, identify individuals at unusually high or low risk, and contribute to global knowledge of the biology of SARS-CoV-2 infection and disease."/><meta data-react-helmet="true" name="theme-color" content="#fff"/><meta data-react-helmet="true" property="og:type" content="business.business"/><meta data-react-helmet="true" property="og:title" content="COVID-19 Host Genetics Initiative"/><meta data-react-helmet="true" property="og:image" content="https://www.covid19hg.org/img/header-4.png"/><meta data-react-helmet="true" property="twitter:card" content="summary_large_image"/><meta data-react-helmet="true" property="twitter:image" content="https://www.covid19hg.org/img/twitter-summary-large.png"/><meta data-react-helmet="true" property="twitter:title" content="COVID-19 Host Genetics Initiative"/><meta data-react-helmet="true" property="twitter:description" content="The COVID-19 host genetics initiative aims to provide support and an analytical network for studies that are broadly interested in identifying genetic determinants of COVID-19 susceptibility and severity. Such discoveries could help to generate hypotheses for drug repurposing, identify individuals at unusually high or low risk, and contribute to global knowledge of the biology of SARS-CoV-2 infection and disease."/><meta data-react-helmet="true" property="og:url" content="https://www.covid19hg.org/projects/"/><style type="text/css"> .gatsby-remark-autolink-headers-class-name.before { position: absolute; top: 0; left: 0; transform: translateX(-100%); padding-right: 4px; } .gatsby-remark-autolink-headers-class-name.after { display: inline-block; padding-left: 4px; } h1 .gatsby-remark-autolink-headers-class-name svg, h2 .gatsby-remark-autolink-headers-class-name svg, h3 .gatsby-remark-autolink-headers-class-name svg, h4 .gatsby-remark-autolink-headers-class-name svg, h5 .gatsby-remark-autolink-headers-class-name svg, h6 .gatsby-remark-autolink-headers-class-name svg { visibility: hidden; } h1:hover .gatsby-remark-autolink-headers-class-name svg, h2:hover 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class="MuiTypography-root MuiTypography-body1">Acknowledgements</p></div></div></div></div><ul class="MuiCollapse-container MuiTreeItem-group MuiCollapse-entered" style="min-height:0px" role="group"><div class="MuiCollapse-wrapper"><div class="MuiCollapse-wrapperInner"><li class="MuiTreeItem-root" role="treeitem" tabindex="-1"><div class="MuiTreeItem-content"><div class="MuiTreeItem-iconContainer"></div><div class="MuiTypography-root MuiTreeItem-label MuiTypography-body1"><div class="jss17"><div class="jss17"><a class="jss19" href="/acknowledgements/"> <!-- -->Project contributors<!-- --> </a></div></div></div></div></li><li class="MuiTreeItem-root" role="treeitem" tabindex="-1"><div class="MuiTreeItem-content"><div class="MuiTreeItem-iconContainer"></div><div class="MuiTypography-root MuiTreeItem-label MuiTypography-body1"><div class="jss17"><div class="jss17"><a class="jss19" href="/publications/"> <!-- -->Publications<!-- --> </a></div></div></div></div></li></div></div></ul></li></ul></div></div><div class="jss14"><div class="jss16"></div><div class="MuiContainer-root jss20 jss21 MuiContainer-fixed MuiContainer-maxWidthLg"><p class="MuiTypography-root MuiTypography-body1"><h4><strong>This page lists projects that are supported by the COVID19 Host Genetics Initiative but they are not part of the centralized efforts because they require specialized approaches or focus on specific patients groups.</strong></h4><h4><strong>As a reminder the centralized analyses are based on <a href="https://docs.google.com/document/d/16ethjgi4MzlQeO0KAW_yDYyUHdB9kKbtfuGW4XYVKQg/edit?usp=sharing">this</a> analysis plan.</strong></h4></p><div class="MuiGrid-root jss22 jss23 MuiGrid-container MuiGrid-spacing-xs-2"><div class="MuiGrid-root jss22 jss24 MuiGrid-item MuiGrid-grid-xs-12"><div class="MuiPaper-root MuiCard-root MuiPaper-elevation1 MuiPaper-rounded"><div class="MuiCardContent-root"><h4 class="MuiTypography-root MuiTypography-h4">Long COVID</h4><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom"><p>Emerging evidence suggests that some patients suffer from various persistent symptoms after the acute phase of COVID-19 infection. The prevalence of this so-called Long COVID, Chronic COVID syndrome (CCS), Post-acute sequelae of COVID-19 (PASC), or Post-COVID-19 syndrome/conditions, is yet to be determined. Given the magnitude of the pandemic, even if only a small proportion of the infected suffer from prolonged sequelae, this will cause a major burden on healthcare systems, individuals and families. </p><p>The “long-haulers” include individuals who had a severe infection in the acute phase as well as those with mild symptoms. A wide spectrum of lingering symptoms have been reported in several organs and tissues, including the lungs, cardiovascular system, pancreas, liver and brain. \ Various pathophysiological mechanisms have been suggested, e.g. tissue destruction, prolonged infection, autoimmune process, and hypercoagulability. Most likely several mechanisms are involved, and patient groups may have very different mechanisms and disease trajectories. </p><p>We have formed an international working group to address the host genetics of this very heterogeneous phenotype, using longitudinal registry data and questionnaires. If you're interested in joining the discussion on how to harmonise phenotypes/diagnoses or questionnaires, or have other ideas on how to collaborate, please join the discussion at our Slack channel or contact Vilma Lammi (<!-- -->[<!-- -->at]helsinki.fi -> to add your information in the study info form and get invited to the working group's meetings and Slack).</p></p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Contact Persons:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom">Vilma Lammi, Hanna M. Ollila, George Davey Smith.</p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Slack Channel:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom">#covid19-hg-longcovid</p></div></div></div><div class="MuiGrid-root jss22 jss25 MuiGrid-item MuiGrid-grid-xs-12"><div class="MuiPaper-root MuiCard-root MuiPaper-elevation1 MuiPaper-rounded"><div class="MuiCardContent-root"><h4 class="MuiTypography-root MuiTypography-h4">WES/WGS working group within the HGI</h4><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom"><p>The COVID-19 pandemic represents an enormous challenge to the world's healthcare systems. The disease is characterized by a highly heterogeneous phenotypic response to SARS-CoV-2 infection, with the large majority of infected individuals having only mild or even no symptoms. However, the severe cases can rapidly evolve towards a critical respiratory distress syndrome and multiple organ failure.</p><p>We believe that the host genetic background plays an important role in COVID-19 susceptibility and progression. Compared to GWAS, WES and WGS have the advantage to bring out both common and very rare variants pinpointing directly to possible severity/protective genes. Both classical gene burden test and innovative analysis using Artificial Intelligence (such as LASSO Regression and Topological Data Analysis) are planned in order to implement a predictive model explaining COVID-19 susceptibility and severity.</p><p>Crucially, we are interested in building an international network of participating cohorts, allowing for larger sample size. Thus, if you would like to join our consortium in order to contribute whole exome or whole genome-sequencing data, please contact us on the ICDA Slack channel below and fill in the cohort description table <a href="https://docs.google.com/spreadsheets/d/1Ah71g2ooPr7r_yqBocmN9LUvuIhyqOn5GOJx3BC9vwA/edit#gid=0">here</a>.</p><p>View previous meeting recordings below:</p><ul><li><a href="https://drive.google.com/file/d/1JWlzWtjBLfMeQsCf8xnvC5QpflPdZDZO/view?usp=sharing">Oct 2, 2020</a></li><li><a href="https://drive.google.com/file/d/1-fdvgIEz3iN2ftMsAdk2B6NNvSXRlKyu/view?usp=sharing">Oct 23, 2020</a></li><li><a href="https://drive.google.com/file/d/1D4mRdgiBDNKQKk0S4piUF6w1r05qQsg0/view?usp=sharing">Nov 12, 2020</a></li><li><a href="https://drive.google.com/file/d/1u4_XTJeYHlQfoGQe31gICAIHZvlv4hg3/view?usp=sharing">Nov 26, 2020</a></li><li><a href="https://drive.google.com/file/d/177IlrmHGKHMZm9xRdgdeJsua_qFn00By/view?usp=sharing">Dec 3, 2020</a></li><li><a href="https://drive.google.com/file/d/19_HPhqTCwC4JK-RwCYUd4Nfp7UruASbz/view?usp=sharing">Dec 17, 2020</a></li><li><a href="https://drive.google.com/file/d/1B547ihhJH0WCSjmJx74Vm0yHqgn5UVVu/view?usp=sharing">Jan 14, 2021</a></li><li><a href="https://drive.google.com/file/d/1QT21NslQKM9SnsF2SJkWToxxL86mfCC1/view?usp=sharing">Jan 21, 2021</a></li><li><a href="https://drive.google.com/file/d/14CIrnHkmTdfuVeN9m4Fk4PS9D_r_tRR9/view?usp=sharing">Jan 28, 2021</a></li><li><a href="https://drive.google.com/file/d/15ZhEJ4_V0iVWL7xXeU13aGAtmvkeOqMU/view?usp=sharing">Feb 4, 2021</a></li><li><a href="https://drive.google.com/file/d/1d70mO4u2qHZOiD6NQ-39NfFLXJan59Dk/view">Feb 11, 2021</a></li><li><a href="https://drive.google.com/file/d/1E6I_3VkteTrh8xZ8j5wo6LdXD-hIY8eo/view">Feb 25, 2021</a></li><li><a href="https://drive.google.com/file/d/1xG4rnLf4JYzuw4tT6MzH0O_rwtF56tCb/view?usp=sharing">Mar 4 2021</a></li><li><a href="https://drive.google.com/file/d/1-RUj0_N7cA0RjjdqHffXhFWw6nh8xr16/view?usp=sharing">Mar 11 2021</a></li><li><a href="https://drive.google.com/file/d/1FxhrqHlM-CN_RmFFNSYyqEPl58HohMjJ/view?usp=sharing">Mar 25 2021</a></li><li><a href="https://drive.google.com/file/d/176C80T83_5mTVIXD8o7MtC-euIqNimkR/view?usp=sharing">Apr 15 2021</a></li><li><a href="https://drive.google.com/file/d/1z5yeSyRVKjZlIxlI81w40mst3ynrdDwg/view">Apr 29 2021</a></li><li><a href="https://drive.google.com/file/d/1nbmasQ_v8sujGpb4vaRc2qIgMdZvXBgp/view?usp=sharing">May 13 2021</a></li><li><a href="https://drive.google.com/file/d/1l4nZXeFoQLgSi8jwhiQ31hE2Ko02Uh-w/view?usp=sharing">Jun 3 2021</a></li><li><a href="https://drive.google.com/file/d/1X6r7x2H8ESOIWPkiyE3aYArEPu3egd77/view">Jul 1 2021</a></li><li><a href="https://drive.google.com/file/d/1Pq0Mgxb2TFmQIG2UN8Ge3HykZjOqcbRt/view">Jul 27 2021</a></li></ul></p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Contact Persons:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom">Alessandra Renieri, Francesca Mari, Brent Richards, Guillaume Butler-Laporte.</p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Slack Channel:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom">#covid19-hg-wes-wgs</p></div></div></div><div class="MuiGrid-root jss22 jss26 MuiGrid-item MuiGrid-grid-xs-12"><div class="MuiPaper-root MuiCard-root MuiPaper-elevation1 MuiPaper-rounded"><div class="MuiCardContent-root"><h4 class="MuiTypography-root MuiTypography-h4">Clonal Hematopoiesis</h4><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom"><p>The presence of pre-existing cardiovascular and lung disease are known to be associated with severe COVID-19. Beyond medical comorbidities, age is a strong independent predictor of COVID-19 severity and may be related to age-related changes in inflammatory cells. Clonal Hematopoiesis is known to alter the inflammatory profile of healthy individuals and may, in part, be a mediator of its ill-effects including cardiovascular disease. Age-related somatic mutations in circulating inflammatory cells have been shown to predispose to chronic inflammatory dysregulation. In some cases, these involve the same pathways implicated in COVID-19. However, whether CH predisposes to severe COVID-19 or affects the complications of COVID-19 is unknown. Conversely, inflammatory stress may be a critical driver of CH. Therefore, studying the acute effects of SARS-CoV-2 infection on the dynamics of CH would provide insight into the potentiators of CH. We seek to understand how clonal hematopoiesis might influence COVID-19 illness severity and conversely how acute infection with SARS-CoV-2 might promote expansion of CHIP.</p><p>paper: <a href="https://www.nature.com/articles/s41591-021-01371-0">https://www.nature.com/articles/s41591-021-01371-0</a><a href="https://www.medrxiv.org/content/10.1101/2020.11.12.20230821v1"></a></p></p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Contact Persons:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom">Philip Awadalla, Pradeep Natarajan, Kelly Bolton.</p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Slack Channel:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom"></p></div></div></div><div class="MuiGrid-root jss22 jss27 MuiGrid-item MuiGrid-grid-xs-12"><div class="MuiPaper-root MuiCard-root MuiPaper-elevation1 MuiPaper-rounded"><div class="MuiCardContent-root"><h4 class="MuiTypography-root MuiTypography-h4">Chr3-clinical trajectories project</h4><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom"><p>The strongest genetic signal for COVID19 severity is located on chromosome 3 and overlaps several genes. However, it is currently unknown 1) which is the likely causal gene and 2) if patients carrying the risk haplotype have different clinical trajectories than those that do not. In this project, we will focus on patients hospitalized for COVID19 and study the association between the chromosomes 3 signal and several longitudinal clinical measures. In particular, we will focus on longitudinal biomarkers, clinical complications/manifestations, and different subtypes of COVID19 patients. The analysis will benefit from combined individual-level data.</p><p>Preprint: <a href="https://www.medrxiv.org/content/10.1101/2021.03.07.21252875v1">https://www.medrxiv.org/content/10.1101/2021.03.07.21252875v1</a><a href="https://www.medrxiv.org/content/10.1101/2020.11.12.20230821v1"></a></p></p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Contact Persons:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom">Brent Richards, Andrea Ganna, Luca Valenti, Alessandra Renieri, Eva Schulte, Hugo Zeberg, Luis Bujanda, Maria Butti, Manuel Romero Gomez, Migeotte Isabelle, Marta Alarcón, Alexandre Pereira, Andre Franke.</p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Slack Channel:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom"></p></div></div></div><div class="MuiGrid-root jss22 jss28 MuiGrid-item MuiGrid-grid-xs-12"><div class="MuiPaper-root MuiCard-root MuiPaper-elevation1 MuiPaper-rounded"><div class="MuiCardContent-root"><h4 class="MuiTypography-root MuiTypography-h4">Acute respiratory distress syndrome</h4><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom"><p>The most severe outcome among COVID-19 cases includes acute respiratory distress syndrome (ARDS) and related respiratory failure that may fall outside of the Berlin definition of ARDS (i.e., ARDS-like respiratory illness) but could still share underlying genetic risk factors. Additionally, while many groups are waiting for genotype data on SARS-CoV-2 infected individuals to be generated, it would be prudent to examine existing data on ARDS (and ARDS-like respiratory illness) in the context of other non-SARS-CoV-2 respiratory viruses and in the context of sepsis.</p><p>The primary research question includes: Which host genetic susceptibility factors are associated with ARDS or ARDS-like phenotypes in the context of respiratory viruses OR sepsis?</p><p>Discovery of these variants will then enable further comparisons with other consortium or investigator-led analyses. For example: Which host genetic susceptibility factors for COVID-19 ARDS are unique to SARS-CoV-2 infection and which ones are shared with ARDS subsequent to other respiratory viruses OR sepsis?</p></p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Contact Persons:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom">Lea Davis, Eric Kerchberger.</p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Slack Channel:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom">#ardsgwas</p></div></div></div><div class="MuiGrid-root jss22 jss29 MuiGrid-item MuiGrid-grid-xs-12"><div class="MuiPaper-root MuiCard-root MuiPaper-elevation1 MuiPaper-rounded"><div class="MuiCardContent-root"><h4 class="MuiTypography-root MuiTypography-h4">COVID19 vascular complications</h4><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom"><p>Recent publications suggest that vascular complications are common in COVID19 patients, especially complications of the ischemic / thrombotic type, and that they may be associated with unfavorable outcomes. In a series of 184 ICU patients admitted in 3 Dutch hospitals with proven COVID-19 pneumonia, 31% developed thrombotic complications, including of imaging-confirmed venous thromboembolism (VTE) in 27% and arterial thrombotic events in 3.7%.</p><p>Two recent French studies have underlined an unexpected high number of VTE (mainly pulmonary embolism - PE) with a prevalence of 16% (64/150) in Strasbourg (3) and 21% (22/107) in Lille despite a conventional thromboprophylaxis in COVID19 patients admitted in ICU. This high increase in PE prevalence which is twice higher than the frequency of PE in the influenza ICU patients may worsen the respiratory prognosis of COVID-19 patients. The low number of associated deep vein thrombosis (DVT)in COVID-19 patients may suggest that they have pulmonary thrombosis rather than embolism. In another recent series of 221 patients with COVID-19 hospitalized in Union hospital, Wuhan, 5% developed acute ischemic stroke (5 large-vessel occlusion, 3 small vessel occlusion, and 3 cardioembolic strokes), 0.5% cerebral venous sinus thrombosis, 0.5% intracerebral hemorrhage.</p><p>While in this and other series COVID19 patients with cerebrovascular complications were significantly older than those without, recent reports from New-York hospitals have described large-vessel strokes as a presenting feature in several young patients. The mechanisms underlying these vascular complications is unclear and could involve excessive inflammation, hypoxia, immobilization and obesity (for VTE), hypercoagulability diffuse intravascular coagulation, cardio-embolism from COVID-19-related cardiac injury and arrhythmia, and possibly invasion of the central nervous system by SARS-CoV-2 leading to encephalopathy. Stroke and VTE genetic predisposition in the general population has been confirmed by recent waves of Genome Wide Association (GWAs) and genetic factors may also modulate the risk of such complications in COVID19 patients. Better understanding the mechanisms underlying the risk of vascular / thrombotic complications in COVID19 patients has important implications for prevention strategies. We aim to identify genetic risk factors associated with the risk of vascular complications (stroke and VTE) in COVID-19 patients, using both an agnostic approach and focusing on known genetic risk factors for these vascular diseases.</p></p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Contact Persons:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom">Israel Fernández Cadenas, Stéphanie Debette, David Alexandre Tregouet.</p><h6 class="MuiTypography-root MuiTypography-h6 MuiTypography-gutterBottom">Slack Channel:</h6><p class="MuiTypography-root MuiTypography-body1 MuiTypography-gutterBottom">#covid19-hg-stroke-vte</p></div></div></div></div><p class="MuiTypography-root MuiTypography-body1"><div class=""></div></p></div></div></div><div id="gatsby-announcer" style="position:absolute;top:0;width:1px;height:1px;padding:0;overflow:hidden;clip:rect(0, 0, 0, 0);white-space:nowrap;border:0" aria-live="assertive" aria-atomic="true"></div></div><script id="gatsby-script-loader">/*<![CDATA[*/window.pagePath="/projects/";/*]]>*/</script><script id="gatsby-chunk-mapping">/*<![CDATA[*/window.___chunkMapping={"polyfill":["/polyfill-b844aa1a0190052d0be8.js"],"app":["/app-e4579ebc6c9b2acbea26.js"],"component---src-pages-404-js":["/component---src-pages-404-js-f242c59d1d8425460d64.js"],"component---src-pages-acknowledgements-js":["/component---src-pages-acknowledgements-js-49a2798576d6b3bacc96.js"],"component---src-pages-blog-index-js":["/component---src-pages-blog-index-js-ca0ef573c9c59408510b.js"],"component---src-pages-contact-index-js":["/component---src-pages-contact-index-js-5aceb39bd7d095498ea8.js"],"component---src-pages-contact-thanks-js":["/component---src-pages-contact-thanks-js-d7ab1c2567da90be793f.js"],"component---src-pages-meeting-archive-js":["/component---src-pages-meeting-archive-js-238dd3ad27c1bf36dd91.js"],"component---src-pages-register-index-js":["/component---src-pages-register-index-js-6fe72f58ed1896926d20.js"],"component---src-pages-results-index-js":["/component---src-pages-results-index-js-81dca442dbfb5e86868d.js"],"component---src-templates-about-page-js":["/component---src-templates-about-page-js-dc974198876df0fe80ed.js"],"component---src-templates-blog-post-js":["/component---src-templates-blog-post-js-e02ec64762e15af6d8cc.js"],"component---src-templates-data-sharing-page-js":["/component---src-templates-data-sharing-page-js-20972066738471cf65ea.js"],"component---src-templates-in-silico-follow-up-page-js":["/component---src-templates-in-silico-follow-up-page-js-c619a1d66dba6c45e15c.js"],"component---src-templates-index-page-js":["/component---src-templates-index-page-js-f79147d44da31a062a0b.js"],"component---src-templates-media-page-js":["/component---src-templates-media-page-js-c77cdf71f99fa9b92f89.js"],"component---src-templates-partners-page-js":["/component---src-templates-partners-page-js-5683a0de0a5af9a647a1.js"],"component---src-templates-projects-page-js":["/component---src-templates-projects-page-js-9673dac31c5e0a7167eb.js"],"component---src-templates-publications-page-js":["/component---src-templates-publications-page-js-f446d460586496a82a9f.js"],"component---src-templates-results-page-js":["/component---src-templates-results-page-js-1bcdb00e2524ed52c9d5.js"]};/*]]>*/</script><script src="/polyfill-b844aa1a0190052d0be8.js" nomodule=""></script><script src="/component---src-templates-projects-page-js-9673dac31c5e0a7167eb.js" async=""></script><script src="/739e68e576ec490a97e0f2a47136acd5d2325c36-0c7e9e68d0feefe25327.js" async=""></script><script src="/058c05dc72c5fc4d312bdb646f92a6e2e01cacce-6115d2bc458585ef9a67.js" async=""></script><script src="/commons-d01780d157e9da7d6e91.js" async=""></script><script src="/app-e4579ebc6c9b2acbea26.js" async=""></script><script src="/532a2f07-cb10b1d521ecd784dc6b.js" async=""></script><script src="/framework-1316094f99f4e494d928.js" async=""></script><script src="/webpack-runtime-99b9c54f1ecc5d4a812b.js" async=""></script></body></html>