Bidirectional relationship between sleep problems and long COVID: a longitudinal analysis of data from the COVIDENCE UK study

Background Studies into the bidirectional relationship between sleep and long COVID have been limited by retrospective pre-infection sleep data and infrequent post-infection follow-up. We therefore used prospectively collected monthly data to evaluate how pre-infection sleep characteristics affect risk of long COVID, and to track changes in sleep duration during the year after SARS-CoV-2 infection. Methods COVIDENCE UK is a prospective, population-based UK study of COVID-19 in adults. We included non-hospitalised participants with evidence of SARS-CoV-2 infection, and estimated odds ratios (ORs) for the association between pre-infection sleep characteristics and long COVID using logistic regression, adjusting for potential confounders. We assessed changes in sleep duration after infection using multilevel mixed models. We defined long COVID as unresolved symptoms at least 12 weeks after infection. We defined sleep quality according to age-dependent combinations of sleep duration and efficiency. COVIDENCE UK is registered with ClinicalTrials.gov, [NCT04330599][1]. Findings We included 3994 participants in our long COVID risk analysis, of whom 327 (8.2%) reported long COVID. We found an inverse relationship between pre-infection sleep quality and risk of long COVID (medium vs good quality: OR 1.37 [95% CI 1.04–1.81]; medium–low vs good: 1.55 [1.12–2.16]; low vs good: 1.94 [1.11–3.38]). Greater variability in pre-infection sleep efficiency was also associated with long COVID (OR per percentage-point increase 1.06 [1.01–1.11]). We assessed post-infection sleep duration in 6860 participants, observing a 0.11 h (95% CI 0.08–0.13) increase in the first month after infection compared with pre-infection, with larger increases for more severe infections. After 1 month, sleep duration largely returned to pre-infection levels, although fluctuations in duration lasted up to 6 months after infection among people reporting long COVID. Interpretation Our findings highlight the bidirectional relationship between sleep and long COVID. While poor-quality sleep before SARS-CoV-2 infection associates with increased risk of long COVID thereafter, changes in sleep duration after infection in these non-hospitalised cases were modest and generally quick to resolve. Funding Barts Charity. ### Competing Interest Statement JB declares consulting fees from PureTech, outside of the submitted work. PEP declares grants paid to their institution from the National Institute for Health and Care Research (NIHR) and UK Research and Innovation (UKRI). All remaining authors declare no competing interests. ### Funding Statement COVIDENCE UK has received support from Barts Charity (MGU0459, MGU0466), Pharma Nord, the Fischer Family Foundation, DSM Nutritional Products, the Epilepsy Foundation, the Karl R Pfleger Foundation, the AIM Foundation, Synergy Biologics, Cytoplan, the UK NIHR Clinical Research Network (52255; 52257), the Health Data Research UK BREATHE Hub, the UKRI Industrial Strategy Challenge Fund (MC\_PC\_19004), Thornton & Ross, Warburtons, Matthew Isaacs (personal donation), Barbara Boucher (personal donation), and Hyphens Pharma. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: COVIDENCE UK was approved by Leicester South Research Ethics Committee (ref 20/EM/0117). All participants gave informed consent to take part in the study before enrolment. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes De-identified participant data will be made upon reasonable request to the corresponding author. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04330599&atom=%2Fmedrxiv%2Fearly%2F2024%2F02%2F08%2F2024.02.08.24302486.atom