Insufficient Sleep Impairs T-Cell Response to SARS-CoV-2

Abstract

Introduction: Considering the unrelenting nature of the COVID-19 global crisis, there is an urgent need to identify modifiable factors that modulate susceptibility and immune responses to SARS-CoV-2, which is also relevant for vaccine response. Insufficient sleep, a highly prevalent and frequently overlooked lifestyle pattern, impairs formation of immunological memory and T cell responses to viral infection, which may influence immune responses to SARS-CoV-2 infection. We hypothesized that objectively monitored, mild sleep restriction (SR) for 6 weeks reduces T cell cross-reactivity to SARS-CoV-2 compared with baseline in healthy individuals. Methods: Ten healthy participants (50% women;40% African-American, 30% White and 30% other), age 42±17 y;BMI 26.8±5.3 kg/m2) with normal habitual sleep duration (7-8 h/night confirmed by 2-week actigraphy screening) underwent 6 weeks of mild SR (1.5 h less than their habitual sleep [HS]) prior to the COVID-19 pandemic. Peripheral blood mononuclear cells (PBMC) were isolated using Ficoll-Paque density-gradient sedimentation from participants at baseline and after 6 weeks of SR. Mean (±SD) sleep duration was 7 h 33 min ± 49 min during HS vs. 6 h ± 38 min during SR (p<0.001). PBMC were cryopreserved in liquid nitrogen until stimulated with SARSCo-V-2 spike glycoprotein peptides (pool 1 = N-terminal and pooI 2 = C-Terminal) for 16 hours. Levels of SARSCoV-2 spike-specific CD4+ (OX40+CD137+) and CD8+ (CD69+CD137+) T cells were quantified by flow cytometry. Levels of cytokines released into supernatant after stimulation with spike peptide pools were quantified using human Th cytokine panel (12-plex) kit (Milipore Sigma). Results: Levels of SARS-CoV-2 spikespecific CD4+ T cells decreased after sleep restriction compared with baseline (pool 1: 0.12±0.02 vs. 0.30±0.08, p=0.04 and pool 2: 0.13±0.02 vs. 0.26±0.05, p=0.02). Similarly, SR reduced levels of SARS-CoV-2 spike-specific CD8+ T cells compared with baseline (pool 1: 0.08±0.01 vs. 0.17±0.04, p=0.07 and pool 2: 0.07±0.01 vs. 0.16±0.03, p=0.04). Levels of IL-13 and IL-22 decreased after SR compared with baseline (p=0.008 and 0.05, respectively). Conclusion: Insufficient sleep reduces T-cell cross-reactivity to SARS-CoV-2 in healthy individuals. Impaired T-cell immunity in insufficient sleep may have implications for COVID-19 susceptibility and immunity as well as vaccine response.