Host factors contributing to susceptibility to COVID-19 disease

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

These studies have been organized as part of a broader effort among multiple principal investigators in the Intramural Research Programs of NIAID and other institutes, as well as a research collaborative agreement with investigators at the American Genome Center/Uniformed Services University of the Health Sciences. We have assembled an international collaboration to study patients enrolled at centers in Italy, which was later expanded to include centers in East Asia, the Middle East, and the Americas. An IRB-approved COVID protocol involving send-in samples was written to facilitate studies at other centers lacking their own COVID protocols. We have partnered with the COVID-Human Genetic Effort, and multiple papers have come out of this international collaboration. In FY 2025, through collaborations with the NIAID COVID-19 Consortium and lead investigators in Germany, we contributed to the identification of increased TGF-beta production during MIS-C as a key step in impaired cellular cytotoxicity, Epstein-Barr virus reactivation, and cytokine storm. This new knowledge provides a potential molecular target for future treatment of MIS-C. Additionally we also contributed to another study that showed that the increased soluble CD13 results in increased NETosis by neutrophils, thereby contributing to the hyperinflammatory features of severe disease. This discovery reveals another potential molecular target for treatment of SARS-CoV-2-infected patients. For both studies, these conclusions were made because we were able to directly study blood samples of the patients collected acutely during their active SARS-CoV-2-related disease phase. Finally, ongoing work led by our research group is investigating the potential role of other genetic variants, including those of dsRNA sensors that initiate type I IFN production in response to virus infection, or host virus restriction factors, in COVID-19 outcome.