Unique immunological profile in patients with COVID-19

Abstract

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-cell immunoglobulin 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 CD56bright and an expansion of mature CD57+ FcεRIγneg 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.

Can Natural Killer Cells Be a Principal Player in Anti-SARS-CoV-2 Immunity?

“…A study that described detailed responses of NK cell to SARS-CoV-2 infection, showed that increased proportions of a subset of NK cell types called adaptive NK cells are found in severe but not moderate COVID-19 disease (55,79). The absolute numbers of NK cells were lower in the blood of patients with COVID-19 compared with healthy controls, consistent with other reports.…”

Single-cell immunophenotyping of the fetal immune response to maternal SARS-CoV-2 infection in late gestation

“…2F) 44,46,47 . There were transcriptional changes associated with exhaustion, such as decreased expression of KLRG1 and SIGLEC7 48 . DGE in NK cells between cases and controls were enriched for genes related to the interferon-alpha response, regulation of NK cell cytokine production, and viral transcription (Fig.…”

Akt-Fas to Quell Aberrant T Cell Differentiation and Apoptosis in Covid-19

“…They still, however, claim their findings suggest that T-cell activation and exhaustion play a role in Covid-19 and posit T-cell targeted treatment options may be of interest (16). Varchetta et al report an increase in TIM-3 and CD69 expression in CD8+ T cells and note the extent of CD8+ T cell lymphopenia was significantly greater in patients that succumbed to Covid-19 (17). They describe this as a hyperactivated/exhausted state and observed that during recovery TIM-3 and CD69 expression on T cells fell and CD8+ lymphocyte count rose.…”

“…They describe this as a hyperactivated/exhausted state and observed that during recovery TIM-3 and CD69 expression on T cells fell and CD8+ lymphocyte count rose. They offer TIM-3, PD-1, and NKG2A as "druggable molecules" that may be used to "unleash antiviral activity" (17).…”