Donna Farber: In vitro and In vivo models to study SARS-Cov2 infection

Summary by: Arooba Ahmed (CC '23)

     Dr. Farber’s group studies immune response to different respiratory viral infections. They now wish to apply their studies to Sars-Cov-2
     The initial virus infection activates type 1 interferon gamma, a protein that is critical for immunity against viral, some bacterial and protozoal infections. Type 1 interferon gamma is also involved in innate immune response and adaptive response. Virus specific C4 cells promote clearance by directly killing viral cells while helper B cells make antibodies which add to clear the virus. The peak of adaptive immune response occurs when the virus is clearing up, where virus specific T-cells and memory B cells have been generated. 
     However, this is in an ideal situation. Depending on the pathogenicity, this can change.  There are different responses to different dosages of the COVID-19 virus. With low dosage there is low morbidity but with high dosage there is little recovery. However, a comparison of viral clearance shows that the virus is cleared with similar kinetics: almost all dosages show clearance by day 12.
     But at day 12, mice with high doses didn't recover even though the virus cleared. The reason could be that even though the mice achieved protection through clearance, the cells became damaged and diseased. This could have resulted in a cytokine storm, where the body starts to attack its own cells. This T-cell immunopathology is dangerous, therefore the group wishes to find an inhibitor to reduce T-cell immunopathology but keep the immunity. 
    They are also looking into tissue resident memory T cells. These are a recently identified lymphocyte lineage that provide a first response against infections re-encountered at body surfaces. They accelerate pathogen clearance and are more protected than regular memory cells. 
     Mouse models with SARS infection show that airway memory cells are protected against SARS-CoV-1. If they are deleted, the protection is lost. In COVID-19 patients, they want to know whether viral clearance is associated with composition or molecular signal of adaptive or innate immunity in the airway. They will obtain respiratory samples and repeat observations over time in longitudinal analysis.
     Currently, they are obtaining respiratory samples from children in the ICU. Most are Respiratory Syncytial Virus (RSV) samples. RSV is a very common, contagious virus that infects the respiratory tract of children. They plan to study airway response over time and observe how T-Cell response in the airway is different from in blood.