Title: The immunologic and virologic determinants of long COVID
Funder: Department of Health and Social Care

Abstract: Long COVID is a largely unexplored disease spectrum of unknown aetiology that occurs in some individuals after recovery from acute infection with SARS-CoV-2. Prevalence rates have been estimated at >10%. In light of the devastating personal and socioeconomic effects of this condition, it is critical that we gain new insights in a timely manner that will inform the diagnosis, pathogenesis, and treatment of long COVID. Our research hypothesis is that long COVID results from the induction of reactive autoimmune diseases as a consequence of cross-reactivity with viral antigens and/or from viral persistence and ongoing immune activation. The overall aim of this project is therefore to identify the immunologic and virologic correlates of long COVID. Clinical assessments will include a detailed history and examination, chest radiographs, exertional oxygen saturations, lung function tests, full blood counts with differentials and screening for active clotting diatheses, biochemical tests, including urea and electrolytes, liver enzymes, indicators of inflammation, such as C-reactive protein and ferritin, and lactate dehydrogenase, and screens for autoantibodies, including specificities associated with neurological conditions. Immunologic assessments will include measurements of inflammatory cytokines and complement components, as well as detailed analyses of innate and adaptive immune responses. Virologic assessments will include direct measurements of viral titers in nasopharyngeal fluid and viral antigen quantification in nasopharyngeal fluid and saliva via qPCR. Samples will be collected both cross-sectionally for comparison with convalescent healthy controls and longitudinally with patient involvement, enabling additional testing during symptom relapses, which are a typical and unexplained feature of long COVID. We anticipate that distinct clinical syndromes will segregate with distinct immunologic and/or virologic parameters, enabling the identification and prospective testing of potential biomarkers, which in turn will inform the development of new diagnostic tests and treatments for long COVID.

Lay abstract: Coronavirus infection has been confirmed in over 157 million people worldwide and over 4 million people in the UK. Initially, there was understandable focus on the care of patients hospitalized with severe disease, but it has subsequently been recognized that many individuals managed their symptoms in the community during the acute phase of COVID-19. The long-term effects of infection in both groups are now becoming apparent. Long COVID describes a broad range of symptoms that persist 12 weeks after acute infection with SARS-CoV-2. Symptoms are diverse and commonly include fatigue, breathlessness, cognitive impairment (&ldquo;brain fog&rdquo;), chest pain, palpitations, and persistent disturbances in smell and taste. Data from the Office for National Statistics suggest that over a million people in the suffer with long COVID in the UK. The potential economic impact and anticipated burden faced by the NHS as a consequence of long COVID has been acknowledged more recently, and a spotlight has been focused on the need for research into the multisystem effects of the condition to inform the future development of diagnostics and therapeutic strategies. Published studies have emphasized the importance of immune responses during acute COVID19. However, little is known about the role of the immune system in long COVID. Our study aims to investigate the hypothesis that overactive or maladaptive immune responses drive ongoing systemic inflammation and clinical symptoms in patients with long COVID.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION