COVID-19 patients are characterized by increased levels of immune cell membrane-bound and soluble CD48

Abstract

Abstract COVID-19 is a respiratory-centered systemic disorder caused by the severe acute respiratory syndrome (SARS-CoV-2) virus. The disease can progress into a severe form causing acute lung injury (ALI), mainly diffuse alveolar damage (DAD) with thromboinflammation, immunopathology, and cytokine storm. CD48 is an activating/co-activating receptor expressed on most hematopoietic cells, existing as both membrane-bound (mCD48) and soluble (sCD48) forms. Its high-affinity ligand is 2B4 (CD244). We previously found the mCD48 and sCD48 levels are dysregulated in asthma patients regardless of their atopic status. Therefore, we reasoned that CD48 could be dysregulated in COVID-19 ALI too. CD48 expression was evaluated in tissue sections collected at autopsies of lethal COVID-19 at the first wave (patients not being exposed to high dose dexamethasone), and on peripheral blood leukocytes and in sera of COVID-19 patients by gene expression profiling (autoimmune panel pf HTG), IHC, flow-cytometry and ELISA. Lung tissue of COVID-19 patients showed significantly increased CD48 mRNA expression and infiltration of CD48+ lymphocytes in comparison to other inflammatory conditions (influenza-virus and pneumococcal pneumonia, and non-COVID-19 DAD). In the peripheral blood mCD48 was significantly increased on all the evaluated cells and, additionally, sCD48 levels were significantly higher in COVID-19 patients independent of disease severity. Positive correlation was found between mCD48 levels on monocytes and sCD48 release. Since both mCD48 and sCD48 are significantly increased in COVID-19, a specific a role for CD48 in COVID-19 can be assumed, suggesting it as a potential target for therapy. Supported by Israel Science Foundation Grant no. 3933/19 the Aimwell Charitable Trust (UK), Emalie Gutterman Memorial Endowed Fund for COPD related research (USA)