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                                                              1. CCRC-HaunerEN
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                                                              Ped-COVID-19 Study

                                                              • Research topics

                                                                • Molecular characterization of COVID-19 infections in children and young adults
                                                                • COVID-19 host genetics
                                                                • Genetic influence on human immune response variation


                                                                Dr. med. Sarah Kim-Hellmuth

                                                                ✉ Sarah.Kimhellmuth@med.uni-muenchen.de

                                                              • COVID-19 is an infectious disease caused by the new strain of coronavirus SARS-CoV-2. It was first identified in 2019 in Wuhan, China, and has since spread globally, resulting in the 2019–20 coronavirus pandemic. Common symptoms include fever and cough, however disease symptoms as well as disease course and outcome are highly variable ranging from asymptomatic cases to severe pneumonia and death. While children are likely to have milder symptoms than adults, children of all ages are susceptible to COVID-19 and can suffer from severe disease. Until now it is unknown why children show a different course of disease compared to adults.

                                                                Studying the immune response to SARS-CoV-2 in children is therefore critical to rapidly advance our understanding of the pathophysiology of COVID-19 both in children and adults. Children offer a unique possibility to study host-related factors that determine COVID-19 severity in the absence of ageing and comorbidity-related interactions, which are largely determining the disease course in adults.

                                                                We have therefore initiated a functional genetics and genomics COVID-19 study to examine the genetic and environmental risk factors of COVID-19 in pediatric and adult patients. Our group integrates deep immune profiling with multi-omics across multiple molecular levels (genome, transcriptome, proteome, metabolome) to enhance our understanding of the human immune response to SARS-CoV-2. Following questions will be addressed:

                                                                - Why does SARS-CoV-2 affect children differently compared to adults?

                                                                - What are the genetic and immunological risk factors that contribute to this difference?

                                                                - Can we use these factors to identify those children who will become severely affected?

                                                                As part of the Child Health Alliance Munich (CHANCE) initiative this prospective study is performed at the Dr. von Hauner Children’s Hospital of the Ludwig-Maximilians University (LMU) Munich and the Department of Pediatrics of the Technical University of Munich School of Medicine (TUM). The study is also actively involved in national (Deutsche COVID-19 OMICS Initiative) and international (COVID-19 Host Genetics Initiative) COVID-19 initiatives to join forces in combating this pandemic.


                                                              • Dr. Sarah Kim-Hellmuth

                                                                Principal Investigator

                                                                ✉  Sarah.Kimhellmuth@med.uni-muenchen.de



                                                                Raffaele Conca

                                                                Manager FACS Facility and Technician

                                                                ✉ Raffaele.Conca@med.uni-muenchen.de


                                                                Sathya Darmalinggam

                                                                Doctoral Researcher

                                                                ✉ Sathya.Darmalinggam@med.uni-muenchen.de

                                                                ☎ 089-4400-57488

                                                                Room: K0.25


                                                                Dr. Anna-Lisa Lanz

                                                                Study doctor

                                                                ✉  AnnaLisa.Lanz@med.uni-muenchen.de



                                                                Dr. Daniel Petersheim

                                                                Study doctor

                                                                ✉ Daniel.Petersheim@med.uni-muenchen.de


                                                                Daniel Bergér

                                                                Doctoral Researcher (PhD track)

                                                                ✉ Daniel.Berger@med.uni-muenchen.de


                                                                Alina Czwienzek

                                                                Doctoral Researcher (MD track)

                                                                ✉ Alina.Czwienzek@med.uni-muenchen.de


                                                                Carola Kaltenhauser

                                                                Doctoral Researcher (MD track)

                                                                ✉  Carola.Kaltenhauser@med.uni-muenchen.de



                                                                Dr. Christina Nickels

                                                                Scientific Project Manager

                                                                ✉ Christina.Nickels@med.uni-muenchen.de

                                                                ☎ 089-4400-57977


                                                                Benedict Wendel

                                                                Doctoral Researcher (MD track)

                                                                ✉ Benedict.Wendel@med.uni-muenchen.de


                                                                Alumni


                                                                Anda Ardeoan

                                                                Modul 6 Student

                                                                ✉  Anda.Ardeoan@med.uni-muenchen.de



                                                                Jöran Sarrazin

                                                                Modul 6 student

                                                                ✉ Joeran.Sarrazin@med.uni-muenchen.de


                                                                Dr. Sepideh Shahkarami

                                                                Postdoctoral Researcher

                                                                ✉ Sepideh.Shahkarami@med.uni-muenchen.de



                                                              • Selected publications:

                                                                1. Flynn, E., Tsu, A., Kasela, S., Kim-Hellmuth, S., Aguet, F., Ardlie, K. G., Bussemaker, H. J., Mohammadi, P. & Lappalainen, T. Transcription factor regulation of eQTL activity across individuals and tissues. Plos Genet 18, e1009719 (2022).

                                                                2. Brandt, M. K., Kim-Hellmuth, S., Ziosi, M., Gokden, A., Wolman, A., Lam, N., Recinos, Y., Hornung, V. K., Schumacher, J. & Lappalainen, T. An autoimmune disease riskvariant: A trans master regulatory effect mediated by IRF1 under immune stimulation? PLoS Genet 17(7), (2021). 

                                                                3. Warnat-Herresthal, S., Schultze, H., Shastry, K. L., Manamohan, S., Mukherjee, S., Garg, V., Sarveswara, R., Händler, K., Pickkers, P., Aziz, N. A., Ktena, S., Tran, F., Bitzer, M., Ossowski, S., Casadei, N., Herr, C., Petersheim, D., Behrends, U., Kern, F., Fehlmann, T., Schommers, P., Lehmann, C., Augustin, M., Rybniker, J., Altmüller, J., Mishra, N., Bernardes, J. P., Krämer, B., Bonaguro, L., Schulte-Schrepping, J., Domenico, E. D., Siever, C., Kraut, M., Desai, M., Monnet, B., Saridaki, M., Siegel, C. M., Drews, A., Nuesch-Germano, M., Theis, H., Heyckendorf, J., Schreiber, S., Kim-Hellmuth, S., […], Deutsche COVID-19 Omics Initiative (DeCOI), Giamarellos-Bourboulis, E. J., Kox, M., Becker, M., Cheran, S., Woodacre, M. S., Goh, E. L. & Schultze, J. L. Swarm Learning for decentralized and confidential clinical machine learning. Nature 1–7 (2021). 

                                                                4. de Goede, O. M., Nachun, D. C., Ferraro, N. M., Gloudemans, M. J., Rao, A. S., Smail, C., Eulalio, T. Y., Aguet, F., Ng, B., Xu, J., Barbeira, A. N., Castel, S. E., Kim-Hellmuth, S., Park, Y., Scott, A. J., Strober, B. J., GTEx Consortium, Brown, C. D., Wen, X., Hall, I. M., Battle, A., Lappalainen, T., Im, H. K., Ardlie, K. G., Mostafavi, S., Quertermous, T., Kirkegaard, K. & Montgomery, S. B. Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease. Cell (2021).

                                                                5. GTEx Consortium#. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369, 1318-1330 (2020). #Lead analyst: Kim-Hellmuth, S.

                                                                6. Kim-Hellmuth, S.†*, Aguet, F.*, Oliva, M., Muñoz-Aguirre, M., Kasela, S., Wucher, V., Castel, S. E., Hamel, A. R., Viñuela, A., Roberts, A. L., Mangul, S., Wen, X., Wang, G., Barbeira, A. N., Garrido-Martin, D., Nadel, B., Zou, Y., Bonazzola, R., Quan, J., Brown, A., Martinez-Perez, A., Soria, J. M., GTEx Consortium, Getz, G., Dermitzakis, E., Small, K. S., Stephens, M., Xi, H. S., Im, H. K., Guigó, R., Segre, A. V., Stranger, B. E., Ardlie, K. G. & Lappalainen, T.  Cell type specific genetic regulation of gene expression across human tissues. Science 369 (2020). 

                                                                7. Oliva, M.*, Muñoz-Aguirre, M.*, Kim-Hellmuth, S.*, Wucher, V., Gewirtz, A., Cotter, D., Parsana, P., Kasela, S., Balliu, B., Viñuela, A., Castel, S. E., Mohammadi, P., Aguet, F., Zou, Y., Khramtsova, E., Skol, A., Garrido-Martin, D., Reverter, F., Brown, A., Evans, P., Gamazon, E., Payne, A., Bonazzola, R., Barbeira, A. N., Hamel, A. R., Martinez-Perez, A., Soria, J. M., GTEx Consortium, Pierce, B., Stephens, M., Eskin, E., Dermitzakis, E., Segre, A. V., Im, H. K., Engelhardt, B., Ardlie, K. G., Montegomery, S., Battle, A., Lappalainen, T., Guigó, R. & Stranger, B. E. The impact of sex on gene expression and its genetic regulation across human tissues. Science 369 (2020). 

                                                                8. Demanelis, K., Jasmine, F., Chen, L. S., Chernoff, M., Tong, L., Delgado, D., Zhang, C., Shinkle, J., Sabarinathan, M., Lin, H., Ramirez, E., Oliva, M., Kim-Hellmuth, S., Stranger, B. E., Lai, T.-P., Aviv, A., Ardlie, K. G., Aguet, F., Ahsan, H., GTEx Consortium, Doherty, J. A., Kibriya, M. G. & Pierce, B. L. Determinants of telomere length across human tissues. Science 369 (2020). 

                                                                9. Kim-Hellmuth, S.*, Hermann, M.*, Eilenberger, J., Ley-Zaporozhan, J., Fischer, M., Hauck, F., Klein, C., Haas, N., Kappler, M., Huebner, J., Jakob, A. & Both, von, U. SARS-CoV-2 Triggering Severe Acute Respiratory Distress Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in a 3-Year-Old Child With Down Syndrome. Journal of the Pediatric Infectious Diseases Society 146, e2020009399–4 (2020).

                                                                10. Kim-Hellmuth, S.†, Bechheim, M., Pütz, B., Mohammadi, P., Nédélec, Y., Giangreco, N., Becker, J., Kaiser, V., Fricker, N., Beier, E., Boor, P., Castel, S. E., Nöthen, M. M., Barreiro, L. B., Pickrell, J. K., Müller-Myhsok, B., Lappalainen, T., Schumacher, J. & Hornung, V. Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations. Nat Commun 8, 266 (2017).

                                                                11. Kim-Hellmuth, S. & Lappalainen, T. Concerted Genetic Function in Blood Traits. Cell 167, 1167–1169 (2016).

                                                                12. Kim, S., Becker, J., Bechheim, M., Kaiser, V., Noursadeghi, M., Fricker, N., Beier, E., Klaschik, S., Boor, P., Hess, T., Hofmann, A., Holdenrieder, S., Wendland, J. R., Fröhlich, H., Hartmann, G., Nöthen, M. M., Müller-Myhsok, B., Pütz, B., Hornung, V. & Schumacher, J. Characterizing the genetic basis of innate immune response in TLR4-activated human monocytes. Nat Commun 5, 5236 (2014).

                                                                13. Kim, S., Kaiser, V., Beier, E., Bechheim, M., Guenthner-Biller, M., Ablasser, A., Berger, M., Endres, S., Hartmann, G. & Hornung, V. Self-priming determines high type I IFN production by plasmacytoid dendritic cells. Eur. J. Immunol. 44, 807–818 (2014).

                                                                14. Kim, S., Bauernfeind, F., Ablasser, A., Hartmann, G., Fitzgerald, K. A., Latz, E. & Hornung, V. Listeria monocytogenes is sensed by the NLRP3 and AIM2 inflammasome. Eur. J. Immunol. 40, 1545–1551 (2010).

                                                                15. Hornung, V., Ellegast, J., Kim, S., Brzózka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K.-K., Schlee, M., Endres, S. & Hartmann, G. 5'-Triphosphate RNA is the ligand for RIG-I. Science 314, 994–997 (2006).

                                                                †Corresponding author, *Equally contributing author

                                                                Complete list of publications

                                                              • 06/2021

                                                                KIT2021


                                                                Carola Kaltenhauser presents her poster at KIT 2021

                                                                Find the abstract here


                                                                05/2021

                                                                Nature


                                                                Our study contributes to a novel swarm learning approach to identify COVID patients

                                                                Read more


                                                                04/2021


                                                                Our 1st Ped-COVID-19 virtual Symposium

                                                                Find the agenda here


                                                                12/2020


                                                                MD student Alina Czwienzek joins the lab



                                                                11/2020


                                                                Our COVID-19 case report in a pediatric patient with Down syndrome is out in JPIDS

                                                                Read more


                                                                10/2020


                                                                PhD student Sathya Darmalinggam joins the lab



                                                                MD student Jöran Sarazzin joins the lab


                                                                09/2020


                                                                Radio report on the GTEx project with Sarah Kim-Hellmuth

                                                                Listen



                                                                Our GTEx Cell Type Group Paper is out in Science

                                                                Read more



                                                                MD student Ben Wendel joins the lab



                                                                The GTEx Main Paper is out in Science

                                                                Read more

                                                                See also the complete list of all GTEx papers



                                                                Our GTEx Sex Group Paper is out in Science

                                                                Read more


                                                                08/2020


                                                                MD student Anda Ardeoan joins the lab


                                                                06/2020


                                                                Sarah Kim-Hellmuth presents her work at ESHG 2020 

                                                                Find out more


                                                                04/2020


                                                                MD Student Carola Kaltenhauser joins the lab 



                                                                News Article covering our Ped-COVID-19 study  

                                                                Find out more



                                                                Ped-COVID-19 study joins the German COVID-19 OMICS Initiative  

                                                                Find out more


                                                                03/2020


                                                                The Ped-COVID-19 study is launched 



                                                                Ped-COVID-19 study joins the international COVID-19 Host Genetics Initiative  

                                                                Find out more


                                                              • Lab picture after our first Ped-COVID-19 symposium

                                                                First lab outing after a long lockdown

                                                              • Ped-COVID-19 Study

                                                                Dr. von Hauner Children's Hospital, University Hospital LMU Munich

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                                                                80337 Munich
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