NATURAL KILLER (NK) CELL DYSFUNCTION, COVID-19 AND IMMUNE DYSREGULATION

Session Type
PLENARY SESSIONS
Date
28.05.2021, Friday
Session Time
12:00 - 14:00
Room
PLENARY HALL
Lecture Time
13:20 - 13:30
Presenter
  • Mo Osman, Canada
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Pre Recorded

Abstract

Background and Aims

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections resulting in coronavirus disease 2019 (COVID-19) is characterized by a clinical constellation consisting of pro-inflammatory cytokine release, organ damage and/or death. Imbalanced immunoregulatory mechanisms during viral infection are potential drivers of this. In this study, we pursued the hypothesis that NK cell dysfunction is a prominent feature of COVID-19 that is associated with a decreased abundance of cytokines required for NK cell functions (e.g. interleukin (IL)15, 12 and 21).

Methods

Only patients with severe COVID-19 were enrolled in our study. Peripheral blood collected within 24-48H of COVID-19 confirmation was used to enumerate NK cells (CD45+CD3-CD56+CD16+/-), CD56bright/dim subsets, and NK-cell functional activities (surface CD107a (degranulation) and intracellular interferon-γ (IFN-γ)) via flow cytometry. Luminex immunoassays were used to determine the serum concentrations of IL12, IL15 and IL21, and soluble CD25 (sCD25)/soluble IL2 receptor α (sIL2-Rα) (R&D Systems Inc). Results from COVID-19 patients were compared with those obtained from healthy controls using Mann-Whitney U statistics. Where applicable, correlation analyses were performed using Spearman rank correlation.

Results

Significantly impaired NK-cell counts and cytolytic activity were observed in COVID-19 patients compared with healthy controls. Also, IL12, IL15, and IL18 were not detected systematically. Serum concentrations of sCD25 were significantly elevated and were inversely correlated with the percentage of NK cells.

Conclusions

Impaired NK-cell cytolytic activity together with elevated sCD25 were consistent with our hypothesis. Together, these findings suggest that impaired counts and cytolytic NK cell activity are important characteristics of severe COVID-19 which can be potentially utilized in future immunomodulatory approaches.

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