What are the hypothetical mechanisms of lymphopenia?
Different mechanisms have been proposed for lymphopenia: 1) T cell exhaustion. The expression of programmed cell death-1 marker (also known as PD-1), which is associated with T-cell exhaustion, was higher in T cells from COVID-19 patients than in healthy controls; the expression of PD-1 and Tim-3 (another exhaustion marker) increased as COVID-19 progressed.64 2) Activation of the P53 signaling in lymphocytes, which suggests a role for apoptosis for in lymphopenia. 3) Lymphocyte pyroptosis, which induces lymphopenia and may be proinflammatory.65 4) T-cell infection with SARS-CoV-2, which may also cause a cytopathic effect on infected T cells. 5) Other mechanisms of lymphopenia that remain to be studied are bone marrow suppression during cytokine storm syndrome (CSS; see below) and sequestration in the lungs during extensive bilateral pneumonia.49