Diane Griffin MD, PhD, Alfred and Jill Sommer Professor and Chair, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health
Annukka (Annie) Antar MD, PhD: Assistant Professor of Medicine, Johns Hopkins Medicine
David Sullivan MD, Professor of molecular microbiology and immunology, Johns Hopkins Bloomberg School of Public Health
A study to determine if immune cells in Long COVID blood are responding to proteins created by the SARS-CoV-2 virus. Antibody-secreting cells are terminally differentiated B cells responsible for large-scale production and secretion of antibodies. The project team will perform a series of experiments to compare numbers of circulating SARS-CoV-2-specific antibody secreting cells, T follicular helper cells, and degree of anti-viral antibody avidity over time (at 3, 6 and 12 months after symptom onset) in individuals with and without Long COVID – at least 50 in each group. Further analysis will also determine if these immune parameters are influenced by treatment received during acute COVID-19 (eg: Remdesivir/Paxlovid/monoclonal antibodies) to indirectly assess whether SARS-CoV-2 clearance can be accelerated.
A central area of Long COVID research is focused on determining if some individuals with the condition do not fully clear the SARS-CoV-2 virus after acute infection (viral reservoir). Instead, the virus may persist in patient tissue where components of the immune system – including B cells and antibodies – continue to be stimulated by its presence. The project team are experts in RNA virus persistence and have extensively studied mechanisms by which RNA viruses such as measles are able to persist after initial infection and impact host immune signaling. Via this research, they have found that measuring the activity of cells involved in germinal center responses – including virus-specific B cells, antibody secreting cells and follicular helper CD4+ T cells – can provide important information on viral persistence. The current study draws from this knoweldgebase to determine if study participants with Long COVID harbor antibody secreting cells or T follicular helper cells that are continuing to respond to SARS-CoV-2 viral proteins, suggesting that such individuals may harbor a viral reservoir. The findings could lead to the development of blood-based biomarkers for SARS-CoV-2 persistence in Long COVID.