IMMUNE ANALYSIS OF LONG COVID TO INFORM RATIONAL CHOICES IN DIAGNOSTIC TESTING AND THERAPEUTICS

Working with the Long COVID (LC) community, the applicants have argued the need for better understanding of the underlying mechanisms. With a more granular understanding of the precise mechanisms underpinning the diverse disease manifestations, one could both implement definitive diagnostic tests (which have been lacking) and identify those pathways implemented in the disease process and better understand the therapeutics likely to be most effective, an approach of 'less observation, more intervention'. Our studies encompass decades of work in autoimmunity, viral immunity, and the interface between the two in infections such as Chikungunya. Our starting point for this study is outreach to individuals who were not hospitalised but now have LC. Investigations start with the assumption that studies to define specific immune mechanisms in blood samples will supply diagnostic tests for healthcare application, as well as pinpointing the known therapeutics most likely to offer successful treatment. We hypothesised that LC may be the result of direct organ damage by the virus, reservoirs of persistent virus (for example in the gut), subsets of white blood cells in the immune system which are dysregulated following infection, or, as in Chikungunya, viral infection has triggered specific autoimmunity - that is, antibodies and/or T cells targeting self tissues to cause symptoms. We will invite study participants through adverts and through support groups, asking them to give a blood sample to look at three specific questions of immune dysregulation: 1. What is the evidence for disrupted white blood cell subsets in LC? 2. What is the evidence for RNA changes in T cells from people with LC, indicating an altered programming as suggested by the many who find that their allergy profile has changed 3. What is the evidence for specific autoimmunity correlated with LC? Deliverable: evidence-based diagnostic tests at the cellular, RNA and autoantibody level