Unique immunological profile in patients with COVID-19

The relationship between severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)and host immunity is poorly understood.We performed an extensive analysis of immune responses in 32 patients with severe COVID-19,some of whom succumbed A control population of healthy subjects was included.Patients with COVID-19 had an altered distribution of peripheral blood lymphocytes,with an increased proportion of mature natural killer(NK)cells and low T-cell numbers.NK cells and CD8^(+)T cells overexpressed T-cellimmunoglobulin and mucin domain-3(TIM-3)and CD69.NK cell exhaustion was attested by increased frequencies of programmed cell death protein 1(PD-1)positive cells and reduced frequencies of natural killer group 2 member D(NKG2D)-,DNAX accessory molecule-1(DNAM-1)-and sialic acid-binding Ig-like lectin 7(Siglec-7)-expressing NK cells,associated with a reduced ability to secrete interferon(IFN)γ.Patients with poor outcome showed a contraction of immature CD56^(bright) and an expansion of mature CD57^(+)F_(CEI)Rlγ^(eng) adaptive NK cells compared to survivors.Increased serum levels of IL-6 were also more frequently identified in deceased patients compared to survivors.Of note,monocytes secreted abundant quantities of IL-6,IL-8,and IL-1β which persisted at lower levels several weeks after recovery with concomitant normalization of CD69,PD-1 and TIM-3 expression and restoration of CD8^(+)T cell numbers.A hyperactivated/exhausted immune response dominate in severe SARS-CoV-2 infection,probably driven by an uncontrolled secretion of inflammatory cytokines by monocytes.These findings unveil a unique immunological profile in COVID-19 patients that will help to design effective stage-specific treatments for this potentially deadly disease.