Project Team

Morgane Bomsel, PhD: Research Director at the French National Centre for Scientific Research (CNRS), Cochin Institute (CNRS, French National Institute for Health and Medical Research (INSERM)/Paris Cité University), France.

Dominique Salmon, MD, PhD: Professor of Infectious and Tropical Diseases, Former Professor of Paris Cité University, France and President of ESPOIRS association (Association for Scientific Trials, Open Partnership in Infectiology, Research and Care on Long COVID).

Emilie Seyrat: Physical and Chemist Engineer, HEC Business Master, Scientific Committee of ESPOIRS association, Paris, France.

Project summary:

Project co-lead Dr. Morgane Bomsel.

The project will determine if replication-competent SARS-CoV-2 virus can be identified in the megakaryocytes (bone marrow-derived cells) and platelets of patients with Long COVID. The presence of viral particles (as measured via a microscope) and the infectivity of identified virus will be established. The project team is also performing a series of experiments to determine if Long COVID plasma contains 1) platelet micro-aggregates and circulating viral proteins such as spike 2) platelets with dysregulated energy metabolism 3) platelets with changes to gene activity profiles compared with platelets isolated from people without symptoms after COVID-19.

Project background:

In May 2020, project team co-lead Dr. Dominique Salmon opened the first Long COVID clinic in Paris, France and started to follow a specific group of 500 patients over time. Samples collected from these patients are being analyzed by a network of scientists at institutions such as the Pasteur Institute and INSERM to delineate Long COVID disease mechanisms. For example, the group identified SARS-CoV-2 RNA in olfactory mucosa tissue of Long COVID patients with cognitive dysfunction and loss of smell. Another study showed that dogs are able to detect volatile organic compounds specific to SARS-CoV-2 active replication in Long COVID patients’ sweat.

The current study – called MEGALONG – expands on these findings to determine if SARS-CoV-2 persistence in platelets and bone marrow cells (megakaryokytes) contributes to Long COVID. Sample analysis is being performed at the Cochin Institute by Dr. Morgane Bomsel, who is widely recognized for her work on megakaryocyte infection and viral propagation by platelets in both acute COVID-19 and chronic HIV. Platelets are small cell fragments in blood that form clots and stop or prevent bleeding. However, they are also part of the immune responses and can engulf viral and bacterial pathogens. Indeed, they have been shown capable of internalizing HIV, dengue virus, hepatitis C virus, influenza virus, and other pathogens.

Confocal microscopy images by the project team showing platelets from acutely SARS-CoV-2 infected individuals contain replicating virus (Zhu et al. 2022).

Platelets are created in the body by large progenitor cells in the bone marrow called megakaryocytes. Several studies show that SARS-CoV-2 can directly infect megakaryocytes. If megakaryocytes become infected, they may “seed” infection of the same patients’ platelets. This could lead to degranulation or deficits in platelet energy metabolism. In addition, because platelets harbor and carry seratonin, platelet infection could contribute to hormonal dysregulation. The current project is analyzing platelet, megakaryocyte, and blood samples from Long COVID patients to determine if persistent SARS-CoV-2 infection of such cells is associated with deregulation (e.g., microclotting), changes in serotonin storage, or altered metabolism. Biological data will be correlated with patient clinical data in a multinomial analysis to define molecular targets associated with Long COVID and to consider targeted treatments. Emilie Seyrat is also maximizing project management.

Top image by the project team: Representative confocal microscopy images after CD41 (green) immunolabeling and replicative SARS-CoV-2 (-) RNA strand in situ hybridization (red) in bone marrow samples obtained from tissue autopsies of three different COVID-19 non-survivors (bar = 10 μm). Arrowheads indicate SARS-CoV-2 (-) RNA inside megakaryokytes. Source: Zhu et al. (2022).