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Abstract
COVID-19 is associated with 5.1% mortality. Although the virological, epidemiological, clinical, and management outcome features of COVID-19 patients have been defined rapidly, the inflammatory and immune profiles require definition as they influence pathogenesis and clinical expression of COVID-19. Here we show lymphopenia, selective loss of CD4+ T cells, CD8+ T cells and NK cells, excessive T-cell activation and high expression of T-cell inhibitory molecules are more prominent in severe cases than in those with mild disease. CD8+ T cells in patients with severe disease express high levels of cytotoxic molecules. Histochemical studies of lung tissue from one fatality show sub-anatomical distributions of SARS-CoV-2 RNA and massive infiltration of T cells and macrophages. Thus, aberrant activation and dysregulation of CD8+ T cells occur in patients with severe COVID-19 disease, an effect that might be for pathogenesis of SARS-CoV-2 infection and indicate that immune-based targets for therapeutic interventions constitute a promising treatment for severe COVID-19 patients.
Immunophenotyping of patients with COVID-19 is ongoing, but much remains to be learned. Here the authors analyze 41 hospitalized patients with COVID-19 and show a higher degree of lymphopenia in various immune cell subsets as well as cytotoxicity and T cell inhibitory marker expression in severe cases compared with mild.
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1 National Clinical Research Center for Infectious Diseases, Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China
2 National Clinical Research Center for Infectious Diseases, Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China; Bengbu Medical College, Department of Clinical Medicine, Bengbu, China (GRID:grid.252957.e) (ISNI:0000 0001 1484 5512)
3 National Clinical Research Center for Infectious Diseases, Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China (GRID:grid.252957.e)
4 National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS- Via Portuense, Rome, Italy (GRID:grid.419423.9) (ISNI:0000 0004 1760 4142)
5 Champalimaud Centre for the Unknown, Immunotherapy Programme, Lisbon, Portugal (GRID:grid.421010.6) (ISNI:0000 0004 0453 9636); University of Mainz, I Med Clinic, Mainz, Germany (GRID:grid.5802.f) (ISNI:0000 0001 1941 7111)
6 University College London, Department of Infection, Division of Infection and Immunity, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); University College London Hospitals NHS Foundation Trust, National Institute for Health Research Biomedical Research Centre, London, UK (GRID:grid.52996.31) (ISNI:0000 0000 8937 2257)
7 National Clinical Research Center for Infectious Diseases, Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China (GRID:grid.52996.31)