Abstract
With a rising incidence of COVID-19-associated morbidity and mortality worldwide, it is critical to elucidate the innate and adaptive immune responses that drive disease severity. We performed longitudinal immune profiling of peripheral blood mononuclear cells from 45 patients and healthy donors. We observed a dynamic immune landscape of innate and adaptive immune cells in disease progression and absolute changes of lymphocyte and myeloid cells in severe versus mild cases or healthy controls. Intubation and death were coupled with selected natural killer cell KIR receptor usage and IgM+ B cells and associated with profound CD4 and CD8 T-cell exhaustion. Pseudo-temporal reconstruction of the hierarchy of disease progression revealed dynamic time changes in the global population recapitulating individual patients and the development of an eight-marker classifier of disease severity. Estimating the effect of clinical progression on the immune response and early assessment of disease progression risks may allow implementation of tailored therapies.
Highlights
Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has infected more than 25 million people worldwide, caused more than 840,000 deaths, and strains health systems on an unprecedented scale
By profiling mild and severe COVID-19 patients and healthy donors with flow cytometry, we demonstrate that SARS-CoV-2 is associated with broad dysregulation of the circulating immune system, characterized by the relative loss of lymphoid cells coupled to expansion of myeloid cells
We conducted an observational study of 45 individuals with COVID19 that were treated at New York Presbyterian Hospital and Lower Manhattan Hospitals, Weill Cornell Medicine (IRB 20-03021645) as in- or outpatients between April and July, 2020
Summary
Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that (as of August 2020) has infected more than 25 million people worldwide, caused more than 840,000 deaths, and strains health systems on an unprecedented scale. The most effective therapeutic approaches developed so far for severe cases involve either general immunosuppression with glucocorticoids (Hennigan & Kavanaugh, 2008) or selective neutralization of IL-6 with tocilizumab (Guaraldi et al, 2020), a monoclonal antibody used to manage cytokine release syndrome in indications such as rheumatoid arthritis (Hennigan & Kavanaugh, 2008). The efficacy of these therapies strongly supports a key role for immune dysregulation in the pathogenesis of COVID-19. In-depth characterization of immune responses to SARS-CoV-2 infection is urgently needed
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