Frank van de Veerdonk has been appointed Professor of Immunotherapy for Infectious Diseases at Radboudumc / Radboud University as of November 1, 2021. He investigates the effect of medications that influence the immune system, in infectious diseases such as influenza, COVID-19 and fungal infections. He tries to rebalance dysregulated mechanisms in the body that lead to disease.
Internist-infectious disease specialist Frank van de Veerdonk of the Department of Internal Medicine found it striking in 2015 that many people with flu admitted to the intensive care unit (ICU) also suffered from infections in the lungs with the fungus Aspergillus. He launched a systematic investigation into this phenomenon and discovered that one in five patients with flu in the ICU was struggling with the fungus, including previously healthy young people. Van de Veerdonk had been researching host defense against fungi such as Candida and Aspergillus for years and sought to find out why these patients are so sensitive to fungal infection.
"We discovered that a virus like influenza can alter host defense creating the ideal conditions for a fungus to strike," Van de Veerdonk explains. "Previously, we only tackled the pathogen in a patient in the ICU with antibiotics for bacterial disease and antifungals for a fungal infection. But we observed that some patients didn't recover well. In this setting immunotherapy can help. These are drugs that rebalance the immune system."
Copying flu research to COVID-19
Immunotherapy has already been extensively studied in patients with rheumatism or cancer. Van de Veerdonk: "These people are chronically ill and therefore you have time to test whether a certain therapy works. In the case of a patient with an infectious disease in the ICU, things advance rapidly and immunotherapy is more difficult to implement. But I think we can gain a lot with immunotherapy regarding the survival and quality of life of these patients."
Van de Veerdonk was busy with his research on fungal infections and immunotherapy in influenza, when COVID-19 emerged. "We were able to copy our research in influenza to this new infectious disease: mapping the patient's host defense, the underlying reasons for susceptibility, the risks of fungal infections and applying immunotherapy." Van de Veerdonk and his team tested the drugs Tocilizumab and Anakinra in a global platform for COVID-19. He is also investigating the use of other types of immunotherapy in infectious diseases, so-called JAK inhibitors, GM-CSF and anti-TNF, and will study immunotherapy in influenza.
Nowadays, van de Veerdonk knows that immunotherapy can work in infectious diseases, but not for every patient. "How can these differences be explained and how can we stratify patients? For example, we discovered that young men in the ICU with COVID-19 have a mutation in TLR7. We now know that they don't clear the virus well, so you must immediately reduce the viral load. Immunotherapy works mainly for subgroups where you know the underlying disease mechanisms and design the immunotherapy accordingly."
Figuring out which patients will benefit from a therapy requires well-organized clinical trials. The same is true if you want to discover which therapy is effective in a new viral disease such as COVID-19. "That organization is very important to me. It would be great if doctors knew the patient’s risk factors, based on blood analysis and genetic screening. Then you can design immunoptherapies and trace family members and, for example, in the case of a TLR7 mutation, vaccinate the family early. Collaboration, communication and networking are crucial here."
Frank van de Veerdonk (Oss, 1975) studied Medicine at the VU. After several years at the Jeroen Bosch Hospital, he started at the Department of Internal Medicine of the Radboudumc in 2005. There he completed his training as an internist in 2011 and obtained his doctorate cum laude in the same year with the title 'The interplay between innate immunity and Th17 responses in Candida infection'. Since then, he has been working at the Radboudumc. He stayed in the United States several times for research, both at the University of Colorado and at St. Jude Children's Hospital in Memphis.
Van de Veerdonk has received many grants for his work, including VENI, VIDI and ZonMW applications. He is also the coordinator of ERARE and Horizon 2020 research projects funded by the European Union. He is closely involved in the European Reference Network for Immune dysregulation, a platform for patients with a rare disorder of the immune system. For the future, Van de Veerdonk focuses on unraveling disease mechanisms and mutations in infectious diseases, the use of immunotherapy, and the organization of clinical trials and optimal patient care.
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