The effect of pre-existing sleep disturbance on T cell responses to SARS-CoV-2 variants, pro-inflammatory and pro-resolving mediators, and glucocorticoid sensitivity in Long COVID.

Sleep disturbance is highly common in Long COVID (LC), and is known to worsen infection outcomes and hinder full recovery from infections. We here investigated whether sleep disturbance prior to SARS-CoV-2 infection compromised inflammatory responses in LC. Blood of 74 participants from the National Institute of Health RECOVER Adult clinical cohort were analyzed at the 6-month time point following the infection. Participants were categorized into groups of Likely, Possible, and No LC based on the Long COVID Research Index. Findings show that Likely LC did not differ from Possible or No LC with respect to interferon-gamma expression in CD4 and CD8 T cells stimulated with omicron spike-peptide variants, the expression of inflammatory mediators by monocytes (IL-6, TNF, COX-2), the ability of glucocorticoids (GC) to suppress inflammatory expression in monocytes, or levels of inflammatory pro-resolving mediators (SPMs). 53% of the Likely LC group reported pre-existing sleep disturbance, compared to 30 and 23% of Possible and No LC groups, respectively. In the Likely LC group, reduced ability of GCs to suppress inflammation was associated pre-existing sleep disturbance, suggesting compromised anti-inflammatory control. Research on the type of sleep disturbance (insomnia, hypersomnia) driving altered GC sensitivity will help to identify LC subtype-specific intervention targets.