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 problems (such as short sleep time, inability to sleep, or problems with the body’s internal clock) are some of the most common and troubling symptoms people with Long COVID report. In this study, researchers wanted to know if having sleep problems before a SARS-CoV-2 (virus that causes COVID-19) infection would affect the immune system’s ability to regulate inflammation. The researchers looked at three parts of the immune response: T cells (which fight viruses), monocytes (which release inflammatory signals—the body’s “danger messages”), and natural compounds (which help regulate inflammation). 

This study analyzed blood samples from 74 adults in the RECOVER adult observational cohort. Participants were included if they (1) had been acutely infected (within 30 days) with a SARS-CoV-2 infection, or (2) were uninfected. Participants were then categorized into groups of Likely Long COVID (LC), Possible LC, and No LC based on the Long COVID Research Index. Slightly more than half of the Likely LC group (53%) reported sleep problems before their SARS-CoV-2 infection, compared with 30% and 23% in the Possible LC and No LC groups, respectively. Overall, the three groups did not show major differences across the immune measures tested. However, researchers found a potentially significant difference in the bodies of people in the Likely LC group who had sleep problems before they got COVID-19. For these people, chemical messengers (hormones) called glucocorticoids were less effective at lowering inflammation.

These findings suggest that the presence of pre-existing sleep disturbance, which has been identified as a risk factor for the development of Long COVID, may compromise the immune system’s ability to regulate inflammation. The authors note important limitations to the study. Sleep problems were measured using a single survey question, so details about the type, severity, or treatment of sleep problems were not available. The study was also small, which limited deeper analyses.

These results, however, point to a promising direction for future research. Understanding which types of sleep disturbance, such as insomnia or excessive sleepiness, affect the body’s inflammatory response could help identify different Long COVID subtypes and guide more targeted treatments. Larger studies with more detailed sleep measurements will be important next steps in turning these early findings into real support for people living with Long COVID.