Corresponding Author: Alexander Hoischen, PhD, Department of Human Genetics and Department of Internal Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, the Netherlands (Alexander.Hoischen@radboudumc.nl).
Accepted for Publication: July 10, 2020.
Published Online: July 24, 2020. doi:10.1001/jama.2020.13719
Author Contributions: Dr Hoischen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs van de Veerdonk and Hoischen contributed equally.
Concept and design: van der Made, Simons, Schuurs-Hoeijmakers, van der Schoot, J. van der Meer, Brunner, Netea, van de Veerdonk, Hoischen.
Acquisition, analysis, or interpretation of data: van der Made, Simons, Schuurs-Hoeijmakers, van den Heuvel, Mantere, Kersten, van Deuren, Steehouwer, van Reijmersdal, Jaeger, Hofste, Astuti, Corominas Galbany, van der Hoeven, Hagmolen of ten Have, Klijn, C. van der Meer, Fiddelaers, de Mast, Bleeker-Rovers, Joosten, Yntema, J. van der Meer, Gilissen, Nelen, Brunner, van de Veerdonk, Hoischen.
Drafting of the manuscript: van der Made, Simons, Schuurs-Hoeijmakers, van Deuren, Steehouwer, van Reijmersdal, Hofste, Astuti, Corominas Galbany, van der Schoot, van der Hoeven, Hagmolen of ten Have, Klijn, C. van der Meer, Fiddelaers, Bleeker-Rovers, Yntema, Nelen, Brunner, van de Veerdonk, Hoischen.
Critical revision of the manuscript for important intellectual content: van der Made, Simons, Schuurs-Hoeijmakers, van den Heuvel, Mantere, Kersten, Jaeger, van der Hoeven, C. van der Meer, de Mast, Joosten, J. van der Meer, Gilissen, Brunner, Netea, van de Veerdonk, Hoischen.
Statistical analysis: van der Made, van Deuren, Gilissen.
Obtained funding: Hoischen.
Administrative, technical, or material support: Simons, Schuurs-Hoeijmakers, van den Heuvel, Kersten, Steehouwer, van Reijmersdal, Jaeger, Hofste, Astuti, Corominas Galbany, van der Schoot, Hagmolen of ten Have, Klijn, C. van der Meer, Fiddelaers, J. van der Meer, Nelen.
Supervision: Schuurs-Hoeijmakers, de Mast, Yntema, J. van der Meer, Netea, van de Veerdonk, Hoischen.
Conflict of Interest Disclosures: Dr Joosten reported being a scientific founder of Trained Therapeutic Discovery and a scientific advisory board member of Olatec Therapeutics. Dr Netea reported being a scientific founder of Trained Therapeutic Discovery and receiving grants from ViiV HealthCare outside the submitted work. No other disclosures were reported.
Funding/Support: Ms Steehouwer and Drs Gillissen, Brunner, and Hoischen are supported by the Solve-RD project. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 779257. Dr Netea was supported by an European Research Council Advanced Grant (No. 833247) and a Spinoza Grant of the Netherlands Organization for Scientific Research. Dr van de Veerdonk was supported by a ZonMW (The Netherlands Organization for Health Research and Development) Vidi grant (No. 91718351). Dr Mantere was supported by the Sigrid Jusélius Foundation. This research was part of the Netherlands X-omics Initiative and partially funded by NWO (The Netherlands Organization for Scientific Research; project 184.034.019) and Radboud Institute for Molecular Life Sciences PhD grants (to Drs Hoischen and Netea).
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank the patients and their families for their participation. We thank Radboud University Medical Center (RUMC) personnel: W. Melchers, PhD; S. D. van der Velde-Visser; M. M. H. M. Jacobs-Camps, M. van de Vorst, BSc; G. Khazeeva, MSc; all colleagues of the multidisciplinary immuno-exome sign-out meeting (MDO); all colleagues of the diagnostic primary immunodeficiency–exome interpretation group, in particular: J. H. S. Diepstra, BSc, E. P. D. Hoenselaar, BSc, and M. Weiss, PhD; the COVID-19 clinical team, in particular: W. Hoefsloot, MD, PhD, J. Hoogerwerf, MD, PhD, M. Reijers, MD, PhD; the Radboud University Medical Center Center for Infectious Diseases (RCI) COVID-19 team; and all colleagues at the Laboratory for Experimental Internal Medicine, in particular H. Lemmers, BSc, F. Weren, MSc, H. Dijkstra, BSc, L. van Emst, BSc, and L. Fransman, BSc. We also thank R. A. Willemze, MD, PhD, Viroscience, Erasmus MC, Rotterdam, the Netherlands. None of the persons indicated above received compensation for their role in the study.
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