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                                                          1. CCRC-HaunerEN
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                                                          Ped-COVID-19 Study

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                                                          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


                                                          Benedict Wendel

                                                          Doctoral Researcher (MD track)

                                                          ✉ Benedict.Wendel@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


                                                          Dr. Sepideh Shahkarami

                                                          Postdoctoral Researcher

                                                          ✉ Sepideh.Shahkarami@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

                                                          Selected publications:

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

                                                          2. 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). doi: 10.1126/science.aaz8528

                                                          3. 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). doi: 10.1126/science.aba3066

                                                          4. 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). doi: 10.1126/science.aaz6876

                                                          5. 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 risk variant has a trans master regulatory effect mediated by IRF1 under immune stimulation. bioRxiv 1–19 (2020). doi:10.1101/2020.02.21.959734

                                                          6. Barbeira, A. N.*, Bonazzola, R.*, Gamazon, E. R.*, Liang, Y.*, Park, Y.*, Kim-Hellmuth, S., Wang, G., Jiang, Z., Zhou, D., Hormozdiari, F., Liu, B., Rao, A., Hamel, A. R., Pividori, M. D., Aguet, F., GTEx GWAS working group, Bastarache, L., Jordan, D. M., Verbanck, M., Do, R., GTEx Consortium, Stephens, M., Ardlie, K., McCarthy, M., Montgomery, S. B., Segre, A. V., Brown, C. D., Lappalainen, T., Wen, X. & Im, H. K. Widespread dose-dependent effects of RNA expression and splicing on complex diseases and traits. bioRxiv 6, e1000888–89 (2019).

                                                          7. de Goede, O. M., Ferraro, N. M., Nachun, D. C., Rao, A. S., Aguet, F., 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., Quertermous, T., Kirkegaard, K. & Montgomery, S. B. Long non-coding RNA gene regulation and trait associations across human tissues. bioRxiv 7, 1860–31 (2019).

                                                          8. 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).

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

                                                          10. Kehrer, C., Hoischen, A., Menkhaus, R., Schwab, E., Müller, A., Kim, S. et al. Whole exome sequencing and array-based molecular karyotyping as aids to prenatal diagnosis in fetuses with suspected Simpson-Golabi-Behmel syndrome. Prenat Diagn 36, 961–965 (2016).

                                                          11. Schäfgen, J., Cremer, K., Becker, J., Kim, S., Aretz, S., Strom, T. M., Wieczorek, D. & Engels, H. De novo nonsense and frameshift variants of TCF20 in individuals with intellectual disability and postnatal overgrowth. European Journal of Human Genetics 24, 1739–1745 (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. Bauernfeind, F., Ablasser, A., Bartok, E., Kim, S., Schmid-Burgk, J., Cavlar, T. & Hornung, V. Inflammasomes: current understanding and open questions. Cell. Mol. Life Sci. 68, 765–783 (2011).

                                                          15. 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).

                                                          16. Bauernfeind, F., Ablasser, A., Kim, S., Bartok, E. & Hornung, V. An unexpected role for RNA in the recognition of DNA by the innate immune system. RNA Biology 7, 151–157 (2010).

                                                          17. Berger, M., Ablasser, A., Kim, S., Bekeredjian-Ding, I., Giese, T., Endres, S., Hornung, V. & Hartmann, G. TLR8-driven IL-12-dependent reciprocal and synergistic activation of NK cells and monocytes by immunostimulatory RNA. J. Immunother. 32, 262–271 (2009).

                                                          18. Ablasser, A., Poeck, H., Anz, D., Berger, M., Schlee, M., Kim, S. et al. Selection of molecular structure and delivery of RNA oligonucleotides to activate TLR7 versus TLR8 and to induce high amounts of IL-12p70 in primary human monocytes. J. Immunol. 182, 6824–6833 (2009).

                                                          19. 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

                                                          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


                                                          Ped-COVID-19 Study

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

                                                          Lindwurmstrasse 4

                                                          80337

                                                          Munich

                                                          0049-89-4400-519821

                                                          0049-89-4400-57418

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                                                          CCRC Hauner

                                                          Kinderklinik und Kinderpoliklinik

                                                          im Dr. von Haunerschen Kinderspital

                                                          Ludwig Maximilians Universität München

                                                          Lindwurmstr. 4

                                                          80337 Munich, Germany

                                                          ☎ +49-89-4400-57705



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