Development of diagnostics characterizing autoantibodies in long COVID cardiovascular dysautonomia

As many as 10% of all subjects with an acute COVID-19 infection will after some months develop a multifaceted syndrome with disabling fatigue, dyspnea, oxygen desaturation at exercise and cardiovascular dysautonomia referred to as long COVID. The typical patient suffering from long COVID is a young or middle-aged woman that frequently has gone from being physically active to becoming so physically disabled that normal life and work is impossible.

A possible clue to the etiology of long COVID has recently come from the observation that subjects suffering from this syndrome frequently develop symptoms that are very similar to the postural orthostatic tachycardia syndrome (POTS), a disease believed to be caused by generation of autoantibodies against G-protein coupled receptors (GPCRs).

The aims of the present study are to:

1. Develop and validate the specificity of ELISAs for autoantibodies binding to the extracellular domain of GPCR of potential relevance for cardiovascular dysautonomia. 2. Determine the presence of such autoantibodies in long COVID patients with and without POTS-like symptoms. 3. Investigate if the presence of GPCR autoantibodies is associated with other long COVID symptoms.

4. Study the effects of these autoantibodies on receptor activity using the GPCR reporter cell lines available to us.

Plasma from POTS patients will be used for the initial development and validation of GPCR autoantibody ELISAs. In collaboration with the long COVID outpatient clinics at Karolinska and SUS we will next investigate if patients with long COVID have GPCR autoantibodies.

Should the present project be able to demonstrate that GPCR autoantibodies are present in subjects with long COVID the ELISA diagnostics described here could relatively rapidly be applied in clinical practise. Even more important the present studies could provide important new information about the pathophysiological mechanisms responsible for development of long COVID and provide the bases for development of therapies.