Jean-Laurent Casanova is interested in identifying monogenic and digenic disorders that selectively compromise immunity to a single infection in otherwise healthy children and adults. Casanova and his team have identified single-gene inborn errors of immunity that selectively underlie one of a variety of viral, bacterial, and fungal infections, including influenza, tuberculosis, and candidiasis. The team also recently studied COVID-19, a potentially life-threatening viral disease. Revealing such monogenic holes in protective immunity has important clinical implications, in terms of diagnosis and treatment, and has important biological significance, by delineating the essential and redundant functions of human genes in host defense.
Scientists have found that cells that line human lungs and other tissues express a protein that can halt SARS-CoV-2 replication before the virus spreads to nearby cells. Their discovery could one day point to new therapeutic strategies to treat or prevent COVID-19, particularly for individuals who are more vulnerable to severe infection. Two new studies offer an explanation for why COVID-19 cases can be so variable. A subset of patients has mutations in key immunity genes; other patients have auto-antibodies that target the same components of the immune system. Both circumstances could contribute to severe forms of the disease. A new international project aims to enroll 500 COVID-19 patients to search for genetic mutations that make some people more vulnerable to severe infection. HHMI scientists are among 84 newly elected members. HHMI researchers identify a rare genetic mutation that tamps down immune response to influenza.