[89Zr]Df-crefmirlimab PET/CT imaging to assess the in vivo distribution of CD8+ T-cells in hospitalized COVID-19 patients

ABSTRACT

Aim/Introduction: COVID-19 patients may present with lymphopenia. The degree of lymphopenia, in particular reduced CD8+ T-cell numbers, is strongly correlated with clinical deterioration and ICU admission [1,2]. It has been postulated that lymphopenia in COVID-19 is caused by;1) sequestration of CD8+ T-cells in peripheral tissues (e.g. lung) [3], 2) accelerated maturation and exhaustion [4,5] or 3) decreased lymphopoiesis [6]. The lack of data on in vivodistribution of CD8+ T-cells hampers a more thorough understanding of this critical prognostic factor. We aim to assess differences in the in vivo distribution of CD8+ T-cells in patients with proven SARS-CoV-2 presenting with lymphopenia or with normal lymphocyte counts, using [89Zr]Df-crefmirlimab PET/CT imaging. Material(s) and Method(s) This is a prospective, observational non-randomized pilot study in hospitalized patients with microbiologically proven SARS-CoV-2 infection. The prior use of immune suppressive medication was an exclusion criterion. Whole body [89Zr]Df-crefmirlimab PET/CT scan were acquired at 24 hrs after intravenous injection of 1.5mg protein dose labelled with 37 MBq (1 mCi)89Zr. Peripheral blood samples were collected for multi-colour flowcytometry to phenotype homing receptors and immune senescence markers, and transcriptomics. Result(s) Three patients were enrolled (all male, average 83 yrs (78-89 yrs)), admitted at 5.3 days (2-10 days) after onset of symptoms and scanned at 2.7 days (2-4 days) after admission. Two patients completed vaccination (2x plus booster), one patient was not vaccinated. Two patients had with lymphocyte count <1.0 x10e9/L and one patient had normal lymphocyte counts on admission. One patient required oxygen suppletion 3L/min. PET/CT scans showed remarkable differences in uptake in the upper respiratory tract versus lower respiratory tract, involvement of distant organs and distribution of CD8+ T-cells across secondary lymphoid organs, spleen and hematopoietic system. Quantification of the scans, flow cytometry and transcriptomic analyses are ongoing. Conclusion(s) In vivo imaging of CD8+ T-cells in hospitalized COVID-19 patients reveals distinct patterns of CD8+ T-cell distribution in early stages of localized infection versus systemic involvement at later stages. Translational data on T-cell phenotyping is currently processed and will be presented.